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The relationship between infection prevalence and host age is informative because it can reveal processes underlying disease dynamics. Most prior work has assumed that age‐prevalence curves are shaped by infection rates, host immunity and/or infection‐induced mortality. Interactions between parasites within a host have largely been overlooked as a source of variation in age‐prevalence curves. We used field survey data and models to examine the role of interspecific interactions between parasites in shaping age‐prevalence curves. The empirical dataset included quantification of parasite infection prevalence for eight co‐occurring trematodes in over 15,000 snail hosts. We characterized age‐prevalence curves for each taxon, examined how they changed over space in relation to co‐occurring trematodes and tested whether the shape of the curves aligned with expectations for the frequencies of coinfections by two taxa in the same host. The models explored scenarios that included negative interspecific interactions between parasites, variation in the force‐of‐infection (FOI) and infection‐induced mortality that varied with host age, which were mechanisms hypothesized to be important in the empirical dataset. In the empirical dataset, four trematode parasites had monotonic increasing age‐prevalence curves and four had unimodal age‐prevalence curves. Some of the curves remained consistent in shape in relation to the prevalence of other potentially interacting trematodes, while some shifted from unimodal to monotonic increasing, suggesting release from negative interspecific interactions. The most common taxa with monotonic increasing curves had lower co‐infection frequencies than expected, suggesting they were competitively dominant. Taxa with unimodal curves had coinfection frequencies that were closer to those expected by chance. The model showed that negative interspecific interactions between parasites can cause a unimodal age‐prevalence curve in the subordinate taxon. Increases in the FOI and/or infection‐induced mortality of the dominant taxon cause shifts in the peak prevalence of the subordinate taxon to a younger host age. Infection‐induced mortality that increased with host age was the only scenario that caused a unimodal curve in the dominant taxon. Results indicated that negative interspecific interactions between parasites contributed to variation in the shape of age‐prevalence curves across parasite taxa and support the growing importance of incorporating interactions between parasites in explaining population‐level patterns of host infection over space and time. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

ABSTRACT Parasites may suppress the immune function of infected hosts using microRNAs (miRNAs) to prevent protein production. Nonetheless, little is known about the diversity of miRNAs and their mode(s) of action. In this study, we investigated the effects of infection by a parasitic lungworm (Rhabdias pseudosphaerocephala) on miRNA and mRNA expression of its host, the invasive cane toad (Rhinella marina). To investigate the cane toad's innate and adaptive immune response to this parasite, we compared miRNA and mRNA expression in naïve toads that had never been infected by lungworms to toads that were infected with lungworms for the first time in their lives, and toads that were infected the second time in their lives (i.e., had two consecutive infections). In total, we identified 101 known miRNAs and 86 potential novel miRNAs. Compared to uninfected and single‐infection toads, multiple‐infection animals drastically downregulated three miRNAs. These miRNAs were associated with gene pathways related to the immune response, potentially reflecting the immunosuppression of cane toads by their parasites. Infected hosts did not respond with substantially differential mRNA transcription; only one gene was differentially expressed between control and single‐infection hosts. Our study suggests that miRNA may play an important role in mediating host–parasite interactions in a system in which an ongoing range expansion by the host has generated substantial divergence in host–parasite interactions. [ABSTRACT FROM AUTHOR]

Helminth infections are a major public health problem as they can cause long-term chronic infections in their hosts for which there is no effective vaccine. During the long-term interaction between helminths and their hosts, helminth-derived extracellular vesicles (EVs) can participate in host immunomodulatory processes by secreting bioactive molecules (BMAs). Growing data suggests that microRNAs (miRNAs) in helminth EVs have a significant impact on the host's immune system. The let-7 family is highly conserved among helminth EVs and highly homologous in the host, and its function in host–parasite crosstalk may reflect active selection for compatibility with the host miRNA machinery. In-depth studies targeting this aspect may better elucidate the mechanism of parasite-host interactions. Hence, this review summarizes the current studies on the cross-species involvement of helminth EV-derived let-7 in host immune regulation and discusses the barriers to related research and potential applications of helminth EVs. [ABSTRACT FROM AUTHOR]

Ocean acidification can negatively affect a broad range of physiological processes in marine shelled molluscs. Marine bioeroding organisms could, in contrast, benefit from ocean acidification due to reduced energetic costs of bioerosion. Ocean acidification could thus exacerbate negative effects (e.g. reduced growth) of ocean acidification and shell borers on oysters. The aim of this study was to assess the impact of ocean acidification on the oyster Ostrea chilensis, the boring sponge Cliona sp., and their host-parasite relationship. We exposed three sets of organisms 1) O. chilensis, 2) Cliona sp., and 3) O. chilensis infested with Cliona sp. to pHT 8.03, 7.83, and 7.63. Reduced pH had no significant effect on calcification, respiration and clearance rate of uninfested O. chilensis. Low pH significantly reduced calcification leading to net dissolution of oyster shells at pHT 7.63 in sponge infested oysters. Net dissolution was likely caused by increased bioerosion by Cliona sp. at pHT 7.63. Additionally, declining pH and sponge infestation had a significant negative antagonistic effect (less negative than predicted additively) on clearance rate. This interaction suggests that sponge infested oysters increase clearance rates to cope with higher energy demand of increased shell repair resulting from higher boring activity of Cliona sp. at low seawater pH. O. chilensis body condition was unaffected by sponge infestation, pH, and the interaction of the two. The reduction in calcification rate suggests sponge infestation and ocean acidification together would exacerbate direct (reduced growth) and indirect (e.g., increased predation) negative effects on oyster health and survival. Our results indicate that ocean acidification by the end of the century could have severe consequences for marine molluscs with boring organisms. [ABSTRACT FROM AUTHOR]

Two key epidemiological parameters, prevalence and mean intensity of infection, together capture the abundance of macroparasite populations, the strength of density-dependent effects they experience, their potential impact on host population dynamics and the selective pressures they exert on their hosts. Yet, the drivers of the extensive variation observed in prevalence and mean intensity of infection, even among related parasite taxa infecting related hosts, remain mostly unknown. We performed phylogenetically grounded Bayesian modelling across hundreds of amphibian populations to test the effects of various predictors of prevalence and intensity of infection by six families of helminth parasites. We focused on the potential effects of key host traits and environmental factors pertinent to focal host populations, i.e. the local diversity of the amphibian community and local climatic variables. Our analyses revealed several important determinants of prevalence or intensity of infection in various parasite families, but none applying to all families. Our study uncovered no universal driver of parasite infection levels, even among parasite taxa from the same phylum, or with similar life cycles and transmission modes. Although local variables not considered here may have effects extending across taxa, our findings suggest the need for a taxon-specific approach in any attempt to predict disease dynamics and impacts in the face of environmental and climatic changes. [ABSTRACT FROM AUTHOR]

This study investigates the biochemical complexity of Hammerschmidtiella diesingi, a parasitic nematode inhabiting the alimentary canal of Periplaneta americana (American cockroach). The protein composition was analyzed using Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE), revealing eight distinct protein bands ranging from 10 to 75 kDa. These bands represent a variety of proteins involved in critical physiological functions, including nutrient absorption, immune evasion and reproduction, enabling the nematode to survive in the host's digestive environment. The 75 kDa band likely corresponds to structural or enzymatic proteins, while the smaller bands (10-25 kDa) may be enzymes involved in digestive processes. The consistency in protein profiles across different sample weights indicates stable protein expression, which is crucial for the nematode's parasitic strategy. The study highlights the evolutionary adaptations of H. diesingi that allow it to grow well in a hostile environment. Future research should focus on functional assays to characterize these proteins and explore genetic mechanisms underlying their expression, which could lead to the development of novel control strategies for parasitic nematode infections in pest species. This research enhances our understanding of the biochemical adaptations of parasitic nematodes and their host interactions. [ABSTRACT FROM AUTHOR]

The Aegle marmelos tree holds immense religious significance in India. Not only do indigenous communities use it, but so do the general populace. Traditional medicine makes use of the whole plant. In addition to its analgesic and antioxidant effects, the plant also possesses antiviral, antifungal, and antibacterial capabilities. The term "Epiphytes" describes the fungal colonies that many endophytic fungi establish on the outside of their host plants. However, there are species that nest in the interstitial and intracellular regions of their host plants; these are known as endophytic species. Endophytes, after interacting with the Bael plant as a host, confer stress tolerance and the capacity to produce bioactive chemicals. It is known that Aegle marmelos include several endophytes. In this study, we detailed the process of isolating ten fungal endophytes from various plant tissues, including bark, roots, fruits, stems and leaves. [ABSTRACT FROM AUTHOR]

Background: Trypanosoma cruzi is transmitted to humans by hematophagous bugs belonging to the Triatominae subfamily. Its intra-vectorial cycle is complex and occurs exclusively in the insect's midgut. Dissecting the elements involved in the cross-talk between the parasite and its vector within the digestive tract should provide novel targets for interrupting the parasitic life cycle and affecting vectorial competence. These interactions are shaped by the strategies that parasites use to infect and exploit their hosts, and the host's responses that are designed to detect and eliminate parasites. The objective of the current study is to characterize the impact of T. cruzi establishment within its vector on the dynamics of its midgut. Methods: In this study, we evaluated the impact of T. cruzi infection on protein expression within the anterior midgut of the model insect Rhodnius prolixus at 6 and 24 h post-infection (hpi) using high-throughput quantitative proteomics. Results: Shortly after its ingestion, the parasite modulates the proteome of the digestive epithelium by upregulating 218 proteins and negatively affecting the expression of 11 proteins involved in a wide array of cellular functions, many of which are pivotal due to their instrumental roles in cellular metabolism and homeostasis. This swift response underscores the intricate manipulation of the vector's cellular machinery by the parasite. Moreover, a more in-depth analysis of proteins immediately induced by the parasite reveals a pronounced predominance of mitochondrial proteins, thereby altering the sub-proteomic landscape of this organelle. This includes various complexes of the respiratory chain involved in ATP generation. In addition to mitochondrial metabolic dysregulation, a significant number of detoxifying proteins, such as antioxidant enzymes and P450 cytochromes, were immediately induced by the parasite, highlighting a stress response. Conclusions: This study is the first to illustrate the response of the digestive epithelium upon contact with T. cruzi, as well as the alteration of mitochondrial sub-proteome by the parasite. This manipulation of the vector's physiology is attributable to the cascade activation of a signaling pathway by the parasite. Understanding the elements of this response, as well as its triggers, could be the foundation for innovative strategies to control the transmission of American trypanosomiasis, such as the development of targeted interventions aimed at disrupting parasite proliferation and transmission within the triatomine vector. [ABSTRACT FROM AUTHOR]

Organismal health and survival depend on the ability to mount an effective immune response against infection. Yet immune defence may be energy-demanding, resulting in fitness costs if investment in immune function deprives other physiological processes of resources. While evidence of costly immunity resulting in reduced longevity and reproduction is common, the role of energy-producing mitochondria on the magnitude of these costs is unknown. Here, we employed Drosophila melanogaster cybrid lines, where several mitochondrial genotypes (mitotypes) were introgressed onto a single nuclear genetic background, to explicitly test the role of mitochondrial variation on the costs of immune stimulation. We exposed female flies carrying one of nine distinct mitotypes to either a benign, heat-killed bacterial pathogen (stimulating immune deployment while avoiding pathology) or to a sterile control and measured lifespan, fecundity, and locomotor activity. We observed mitotype-specific costs of immune stimulation and identified a positive genetic correlation in immune-stimulated flies between lifespan and the proportion of time cybrids spent moving while alive. Our results suggests that costs of immunity are highly variable depending on the mitochondrial genome, adding to a growing body of work highlighting the important role of mitochondrial variation in host–pathogen interactions. [ABSTRACT FROM AUTHOR]

Abstract Sleep is a complex and conserved biological process that affects several body functions and behaviors. Evidence suggests that there is a reciprocal interaction between sleep and immunity. For instance, fragmented sleep can increase the probability of parasitic infections and reduce the ability to fight infections. Moreover, viral and bacterial infections alter the sleep patterns of infected individuals. However, the effects of macro-parasitic infections on sleep remain largely unknown, and measuring sleep in non-model organisms remains challenging. In this study, we investigated whether macro-parasite infections could alter sleep-like behavior of their hosts. We experimentally infected three-spined sticklebacks (Gasterosteus aculeatus), a freshwater fish, with the tapeworm Schistocephalus solidus and used a hidden Markov model to characterize sleep-like behavior in sticklebacks. One to four days after parasite exposure, infected fish showed no difference in sleep-like behavior compared with non-exposed fish, and fish that were exposed-but-not-infected only showed a slight reduction in sleep-like behavior during daytime. Twenty-nine to 32 days after exposure, infected fish showed more sleep-like behavior than control fish, while exposed-but-not-infected fish showed overall less sleep-like behavior. Using brain transcriptomics, we identified immune- and sleep-associated genes that potentially underlie the observed behavioral changes. These results provide insights into the complex association between macro-parasite infection, immunity, and sleep in fish and may thus contribute to a better understanding of reciprocal interactions between sleep and immunity.

Abstract Background Trypanosoma cruzi is transmitted to humans by hematophagous bugs belonging to the Triatominae subfamily. Its intra-vectorial cycle is complex and occurs exclusively in the insect's midgut. Dissecting the elements involved in the cross-talk between the parasite and its vector within the digestive tract should provide novel targets for interrupting the parasitic life cycle and affecting vectorial competence. These interactions are shaped by the strategies that parasites use to infect and exploit their hosts, and the host's responses that are designed to detect and eliminate parasites. The objective of the current study is to characterize the impact of T. cruzi establishment within its vector on the dynamics of its midgut. Methods In this study, we evaluated the impact of T. cruzi infection on protein expression within the anterior midgut of the model insect Rhodnius prolixus at 6 and 24 h post-infection (hpi) using high-throughput quantitative proteomics. Results Shortly after its ingestion, the parasite modulates the proteome of the digestive epithelium by upregulating 218 proteins and negatively affecting the expression of 11 proteins involved in a wide array of cellular functions, many of which are pivotal due to their instrumental roles in cellular metabolism and homeostasis. This swift response underscores the intricate manipulation of the vector's cellular machinery by the parasite. Moreover, a more in-depth analysis of proteins immediately induced by the parasite reveals a pronounced predominance of mitochondrial proteins, thereby altering the sub-proteomic landscape of this organelle. This includes various complexes of the respiratory chain involved in ATP generation. In addition to mitochondrial metabolic dysregulation, a significant number of detoxifying proteins, such as antioxidant enzymes and P450 cytochromes, were immediately induced by the parasite, highlighting a stress response. Conclusions This study is the first to illustrate the response of the digestive epithelium upon contact with T. cruzi, as well as the alteration of mitochondrial sub-proteome by the parasite. This manipulation of the vector's physiology is attributable to the cascade activation of a signaling pathway by the parasite. Understanding the elements of this response, as well as its triggers, could be the foundation for innovative strategies to control the transmission of American trypanosomiasis, such as the development of targeted interventions aimed at disrupting parasite proliferation and transmission within the triatomine vector. Graphical Abstract

Abstract Background Schistosomiasis is a parasitic disease caused by trematodes of the genus Schistosoma. The intravascular worms acquire the nutrients necessary for their survival from host blood. Since all animals are auxotrophic for riboflavin (vitamin B2), schistosomes too must import it to survive. Riboflavin is an essential component of the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD); these support key functions of dozens of flavoenzymes. Methods Here, using a combination of metabolomics, enzyme kinetics and in silico molecular analysis, we focus on the biochemistry of riboflavin and its metabolites in Schistosoma mansoni (Sm). Results We show that when schistosomes are incubated in murine plasma, levels of FAD decrease over time while levels of FMN increase. We show that live schistosomes cleave exogenous FAD to generate FMN and this ability is significantly blocked when expression of the surface nucleotide pyrophosphatase/phosphodiesterase ectoenzyme SmNPP5 is suppressed using RNAi. Recombinant SmNPP5 cleaves FAD with a Km of 178 ± 5.9 µM and Kcat/Km of 324,734 ± 36,347 M− 1.S− 1. The FAD-dependent enzyme IL-4I1 drives the oxidative deamination of phenylalanine to produce phenylpyruvate and H2O2. Since schistosomes are damaged by H2O2, we determined if SmNPP5 could impede H2O2 production by blocking IL-4I1 action in vitro. We found that this was not the case; covalently bound FAD on IL-4I1 appears inaccessible to SmNPP5. We also report that live schistosomes can cleave exogenous FMN to generate riboflavin and this ability is significantly impeded when expression of a second surface ectoenzyme (alkaline phosphatase, SmAP) is suppressed. Recombinant SmAP cleaves FMN with a Km of 3.82 ± 0.58 mM and Kcat/Km of 1393 ± 347 M− 1.S− 1. Conclusions The sequential hydrolysis of FAD by tegumental ecto-enzymes SmNPP5 and SmAP can generate free vitamin B2 around the worms from where it can be conveniently imported by the recently described schistosome riboflavin transporter SmaRT. Finally, we identified in silico schistosome homologs of enzymes that are involved in intracellular vitamin B2 metabolism. These are riboflavin kinase (SmRFK) as well as FAD synthase (SmFADS); cDNAs encoding these two enzymes were cloned and sequenced. SmRFK is predicted to convert riboflavin to FMN while SmFADS could further act on FMN to regenerate FAD in order to facilitate robust vitamin B2-dependent metabolism in schistosomes.

Extracellular vesicles (EVs) have emerged as key intercellular communication and pathogenesis mediators. Parasitic organisms' helminths, causewidespread infections with significant health impacts worldwide. Recent research has shed light on the role of EVs in the lifecycle, immune evasion, and disease progression of these parasitic organisms. These tiny membrane-bound organelles including microvesicles and exosomes, facilitate the transfer of proteins, lipids, mRNAs, and microRNAs between cells. EVs have been isolated from various bodily fluids, offering a potential diagnostic and therapeutic avenue for combating infectious agents. According to recent research, EVs from helminths hold great promise in the diagnosis of parasitic infections due to their specificity, early detection capabilities, accessibility, and the potential for staging and monitoring infections, promote intercellular communication, and are a viable therapeutic tool for the treatment of infectious agents. Exploring host-parasite interactions has identified promising new targets for diagnostic, therapy, and vaccine development against helminths. This literature review delves into EVS's origin, nature, biogenesis, and composition in these parasitic organisms. It also highlights the proteins and miRNAs involved in EV release, providing a comprehensive summary of the latest findings on the significance of EVs in the biology of helminths, promising targets for therapeutic and diagnostic biomarkers. [ABSTRACT FROM AUTHOR]

Dactylogyrosis is caused by more than 900 reported species of Dactylogyrus (gill fluke), mostly in Cyprinoidei fish leading to low to severe mortality in different culture systems and also in rivers/lakes. Dactylogyrus has been reported worldwide where Cyprinoidei is endemic. In recent years, incidents of infection and infectivity of different species of Dactylogyrus have increased many-fold due to several predisposing factors like intensification of culture, environmental quality, climatic change, poor quality fish seed, etc. These parasites are host choosy, either generalist or specialist. Dactylogyrus infection causes major changes in the anatomy and physiology of gill function. Necrosis, hyperplasia and hypertrophy of gill lamellae are the common pathologies observed during infection, which in turn invites other secondary pathogens leading to heavy mortalities. Currently, very few drugs or chemicals are available for controlling dactylogyrosis. Very few attempts have been made to develop vaccines against this important parasite. Here, we review the innate and adaptive immune responses modulated by Dactylogyrus infection and a hypothetical immunological model has been proposed to understand host-pathogen interaction based on our findings. The information collected and analysed in this review on the biology and host-pathogen interaction will help in the development of prophylactic and other sustainable management measures to reduce the loss associated with dactylogyrosis. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are a class of small regulatory RNA that are generated via core protein machinery. The miRNAs direct gene-silencing mechanisms to mediate an essential role in gene expression regulation. In mollusks, miRNAs have been demonstrated to be required to regulate gene expression in various biological processes, including normal development, immune responses, reproduction, and stress adaptation. In this study, we aimed to establishment the requirement of the miRNA pathway as part of the molecular response of exposure of Biomphalaria glabrata (snail host) to Schistosoma mansoni (trematode parasite). Initially, the core pieces of miRNA pathway protein machinery, i.e., Drosha, DGCR8, Exportin-5, Ran, and Dicer, together with the central RNA-induced silencing complex (RISC) effector protein Argonaute2 (Ago2) were elucidated from the B. glabrata genome. Following exposure of B. glabrata to S. mansoni miracidia, we identified significant expression up-regulation of all identified pieces of miRNA pathway protein machinery, except for Exportin-5, at 16 h post exposure. For Ago2, we went on to show that the Bgl-Ago2 protein was localized to regions surrounding the sporocysts in the digestive gland of infected snails 20 days post parasite exposure. In addition to documenting elevated miRNA pathway protein machinery expression at the early post-exposure time point, a total of 13 known B. glabrata miRNAs were significantly differentially expressed. Of these thirteen B. glabrata miRNAs responsive to S. mansoni miracidia exposure, five were significantly reduced in their abundance, and correspondingly, these five miRNAs were determined to putatively target six genes with significantly elevated expression and that have been previously associated with immune responses in other animal species, including humans. In conclusion, this study demonstrates the central importance of a functional miRNA pathway in snails, which potentially forms a critical component of the immune response of snails to parasite exposure. Further, the data reported in this study provide additional evidence of the complexity of the molecular response of B. glabrata to S. mansoni infection: a molecular response that could be targeted in the future to overcome parasite infection and, in turn, human schistosomiasis. [ABSTRACT FROM AUTHOR]

The study of host–parasite co‐evolution is a central topic in evolutionary ecology. However, research is still fragmented and the extent to which parasites influence host life history is debated. One reason for this incomplete picture is the frequent omission of environmental conditions in studies analyzing host–parasite dynamics, which may influence the exposure to or effects of parasitism. To contribute to elucidating the largely unresolved question of how environmental conditions are related to the prevalence and intensity of infestation and their impact on hosts, we took advantage of 25 years of monitoring of a breeding population of pied flycatchers, Ficedula hypoleuca, in a Mediterranean area of central Spain. We investigated the influence of temperature and precipitation during the nestling stage at a local scale on the intensity of blowfly (Protocalliphora azurea) parasitism during the nestling stage. In addition, we explored the mediating effect of extrinsic and intrinsic factors and blowfly parasitism on breeding success (production of fledglings) and offspring quality (nestling mass on day 13). The prevalence and intensity of blowfly parasitism were associated with different intrinsic (host breeding date, brood size) and extrinsic (breeding habitat, mean temperature) factors. Specifically, higher average temperatures during the nestling phase were associated with lower intensities of parasitism, which may be explained by changes in blowflies’ activity or larval developmental success. In contrast, no relationship was found between the prevalence of parasitism and any of the environmental variables evaluated. Hosts that experienced high parasitism intensities in their broods produced more fledglings as temperature increased, suggesting that physiological responses to severe parasitism during nestling development might be enhanced in warmer conditions. The weight of fledglings was, however, unrelated to the interactive effect of parasitism intensity and environmental conditions. Overall, our results highlight the temperature dependence of parasite–host interactions and the importance of considering multiple fitness indicators and climate‐mediated effects to understand their complex implications for avian fitness and population dynamics. [ABSTRACT FROM AUTHOR]

Background: Clonorchiasis remains a serious public health problem. However, the molecular mechanism underlying clonorchiasis remains largely unknown. Amino acid (AA) metabolism plays key roles in protein synthesis and energy sources, and improves immunity in pathological conditions. Therefore, this study aimed to explore the AA profiles of spleen in clonorchiasis and speculate the interaction between the host and parasite. Methods: Here targeted ultrahigh performance liquid chromatography multiple reaction monitoring mass spectrometry was applied to discover the AA profiles in spleen of rats infected with Clonorchis sinensis. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis (KEGG) was performed to characterize the dysregulated metabolic pathways. Results: Pathway analysis revealed that phenylalanine, tyrosine, and tryptophan biosynthesis and β-alanine metabolism were significantly altered in clonorchiasis. There were no significant correlations between 14 significant differential AAs and interleukin (IL)-1β. Although arginine, asparagine, histidine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine were positively correlated with IL-6, IL-10, tumor necrosis factor (TNF)-α as well as aspartate aminotransferase and alanine aminotransferase; β-alanine and 4-hydroxyproline were negatively correlated with IL-6, IL-10, and TNF-α. Conclusion: This study reveals the dysregulation of AA metabolism in clonorchiasis and provides a useful insight of metabolic mechanisms at the molecular level. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is a parasitic disease caused by trematodes of the genus Schistosoma. The intravascular worms acquire the nutrients necessary for their survival from host blood. Since all animals are auxotrophic for riboflavin (vitamin B2), schistosomes too must import it to survive. Riboflavin is an essential component of the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD); these support key functions of dozens of flavoenzymes. Methods: Here, using a combination of metabolomics, enzyme kinetics and in silico molecular analysis, we focus on the biochemistry of riboflavin and its metabolites in Schistosoma mansoni (Sm). Results: We show that when schistosomes are incubated in murine plasma, levels of FAD decrease over time while levels of FMN increase. We show that live schistosomes cleave exogenous FAD to generate FMN and this ability is significantly blocked when expression of the surface nucleotide pyrophosphatase/phosphodiesterase ectoenzyme SmNPP5 is suppressed using RNAi. Recombinant SmNPP5 cleaves FAD with a Km of 178 ± 5.9 µM and Kcat/Km of 324,734 ± 36,347 M− 1.S− 1. The FAD-dependent enzyme IL-4I1 drives the oxidative deamination of phenylalanine to produce phenylpyruvate and H2O2. Since schistosomes are damaged by H2O2, we determined if SmNPP5 could impede H2O2 production by blocking IL-4I1 action in vitro. We found that this was not the case; covalently bound FAD on IL-4I1 appears inaccessible to SmNPP5. We also report that live schistosomes can cleave exogenous FMN to generate riboflavin and this ability is significantly impeded when expression of a second surface ectoenzyme (alkaline phosphatase, SmAP) is suppressed. Recombinant SmAP cleaves FMN with a Km of 3.82 ± 0.58 mM and Kcat/Km of 1393 ± 347 M− 1.S− 1. Conclusions: The sequential hydrolysis of FAD by tegumental ecto-enzymes SmNPP5 and SmAP can generate free vitamin B2 around the worms from where it can be conveniently imported by the recently described schistosome riboflavin transporter SmaRT. Finally, we identified in silico schistosome homologs of enzymes that are involved in intracellular vitamin B2 metabolism. These are riboflavin kinase (SmRFK) as well as FAD synthase (SmFADS); cDNAs encoding these two enzymes were cloned and sequenced. SmRFK is predicted to convert riboflavin to FMN while SmFADS could further act on FMN to regenerate FAD in order to facilitate robust vitamin B2-dependent metabolism in schistosomes. [ABSTRACT FROM AUTHOR]

SigE is one of the main regulators of mycobacterial stress response and is characterized by a complex regulatory network based on two pathways, which have been partially characterized in conditions of surface stress. The first pathway is based on the induction of sigE transcription by the two-component system MprAB, while the second is based on the degradation of SigE antisigma factor RseA by ClpC1P2, a protease whose structural genes are induced by ClgR. We characterized the dynamics of the SigE network activation in conditions of surface stress and low pH in Mycobacterium tuberculosis. Using a series of mutants in which the main regulatory nodes of the network have been inactivated, we could explore their hierarchy, and we determined that MprAB had a key role in the network activation in both stress conditions through the induction of sigE. However, while in conditions of surface stress the absence of MprAB totally abrogated sigE induction, under low pH conditions it only resulted in a small delay of the induction of sigE. In this case, sigE induction was due to SigH, which acted as a MprAB backup system. The ClgR pathway, leading to the degradation of the SigE anti-sigma factor RseA, was shown to be essential for the activation of the SigE network only following surface stress, where it showed an equal hierarchy with the MprAB pathway. [ABSTRACT FROM AUTHOR]

The protozoan parasite Plasmodium, the causative agent of malaria, undergoes an obligatory stage of intra‐hepatic development before initiating a blood‐stage infection. Productive invasion of hepatocytes involves the formation of a parasitophorous vacuole (PV) generated by the invagination of the host cell plasma membrane. Surrounded by the PV membrane (PVM), the parasite undergoes extensive replication. During intracellular development in the hepatocyte, the parasites provoke the Plasmodium‐associated autophagy‐related (PAAR) response. This is characterized by a long‐lasting association of the autophagy marker protein, and ATG8 family member, LC3B with the PVM. LC3B localization at the PVM does not follow the canonical autophagy pathway since upstream events specific to canonical autophagy are dispensable. Here, we describe that LC3B localization at the PVM of Plasmodium parasites requires the V‐ATPase and its interaction with ATG16L1. The WD40 domain of ATG16L1 is crucial for its recruitment to the PVM. Thus, we provide new mechanistic insight into the previously described PAAR response targeting Plasmodium liver stage parasites. [ABSTRACT FROM AUTHOR]

Parasites represent a critically understudied component of reef communities—a knowledge gap that has become more evident as infectious diseases emerge. Here, we test the roles of competing ecological and evolutionary factors in driving infections by an emerging infectious phenomenon: Black spot syndrome (BSS) in Caribbean reef fishes. BSS, a condition associated with localized hyperpigmentation in the dermis and fins of fishes, has recently been linked to infection by trematode parasites in the genus Scaphanocephalus. Using phylogenetic generalized linear mixed models, we evaluated the influence of host phylogeny, habitat preference, body size, and trophic position on infection abundance. Metacercariae of Scaphanocephalus were recorded in 29 of 41 fish species, including 21 new host species records, and within 306 fish (62.3% prevalence). Among species, infection load increased significantly with host body size and decreased with host trophic level, such that large-bodied herbivores tended to support the most infection. There was no significant effect of host phylogeny on infection load. These results suggest the parasite is a generalist in its use of fish intermediate hosts and emphasize the influence of local variation in parasite exposure risk. Overall, the count of visible spots per fish was a positive predictor of Scaphanocephalus abundance among species and individuals, although not all fish species exhibited spots, even when infection loads were high. Findings from this study indicate that Scaphanocephalus infections are far more prevalent in reef fishes than previously recognized and highlight the importance of investigating infection patterns beyond the external symptoms of BSS. [ABSTRACT FROM AUTHOR]

Apis cerana is the original host of Vairimorpha (Nosema) ceranae, a widespread fungal parasite that causes bee nosemosis, which severely threatens the health of bee colonies and the sustainable development of the apiculture industry. To evaluate the impact of V. ceranae infection on A. c. cerana workers, V. ceranae spores were purified and used to inoculate newly emerged workers to evaluate the effects of V. ceranae infection. This was followed by an in-depth investigation of V. ceranae spore load and host sucrose solution consumption. Activities of four major antioxidant enzymes (SOD, PPO, CAT, and GST) were determined. Paraffin sections of the host midgut tissue were prepared and subjected to microscopic observation. The survival rates of V. ceranae-inoculated and uninoculated workers were analyzed. The results showed that spore load gradually increased and peaked at 12 dpi. The consumption of workers in the V. ceranae-inoculated group was extremely significant higher (P < 0.0001) than that of workers in the un-inoculated group. The results of antioxidant enzyme activity were suggestive of positive host defense via catalase (CAT) and glutathione-S-transferase (GST) in the middle stage of infection, as well as the negative fungal impact on superoxide dismutase (SOD) and polyphenol oxidase (PPO) at the whole stage of infection, reflecting the complex host-parasite interaction. Additionally, we observed a disruption in the structure of the host midgut epithelial cells. Moreover, the survival rate of workers in V. ceranae-inoculated groups was nearly always lower than that of workers in the uninoculated groups. These results demonstrate a consistent increase in spore load with the proliferation of V. ceranae, leading to persistent energetic stress and midgut epithelial cell structural damage to the host, ultimately resulting in a shortened lifespan for the host. Our findings enhance the current understanding of the interactions between A. cerana and V. ceranae as well as provide a solid basis for exploring the mechanisms underlying host response and V. ceranae infection.

Cigarette butts (CBs), of which around 4.5 trillion are discarded annually, are one of the most common types of litter worldwide. CBs contain various chemicals, including metals, nicotine, and polycyclic aromatic hydrocarbons, which can leach into water and pose a threat to aquatic organisms such as cyanobacteria and chytrid fungi. Chytrids, zoosporic fungi that parasitize cyanobacteria lethally, play a crucial role in regulating cyanobacteria blooms by delaying or suppressing bloom formation. Despite the prevalence of CBs in the environment, the impact of their leachates on cyanobacteria-chytrid interactions is not well understood. We assessed the effects of CB leachate on the interaction between the toxigenic cyanobacterium Planktothrix agardhii and its chytrid parasite Rhizophydium megarrhizum. CB leachate inhibited cyanobacterial growth in uninfected cultures. Infection prevalence decreased at 0.2, 2, and 10 CB L−1, with the two highest concentrations completely suppressing infection. Interestingly, at the highest CB concentration, cyanobacterial biomass in infected cultures was comparable to that of uninfected cultures not exposed to CB leachate, suggesting that the presence of chytrids mitigates the impact of the leachate. This study demonstrates that CB leachates are a potential environmental hazard that can enable cyanobacterial growth by inhibiting chytrid infections during epidemics. In addition, our research highlights the importance of assessing the effects of chemical mixtures, such as those leached from CBs, on multi-species interactions, such as host-parasite dynamics. These assessments are crucial to better understand the impact of pollutants on aquatic ecosystems.

Helminth infections are a major public health problem as they can cause long-term chronic infections in their hosts for which there is no effective vaccine. During the long-term interaction between helminths and their hosts, helminth-derived extracellular vesicles (EVs) can participate in host immunomodulatory processes by secreting bioactive molecules (BMAs). Growing data suggests that microRNAs (miRNAs) in helminth EVs have a significant impact on the host’s immune system. The let-7 family is highly conserved among helminth EVs and highly homologous in the host, and its function in host–parasite crosstalk may reflect active selection for compatibility with the host miRNA machinery. In-depth studies targeting this aspect may better elucidate the mechanism of parasite-host interactions. Hence, this review summarizes the current studies on the cross-species involvement of helminth EV-derived let-7 in host immune regulation and discusses the barriers to related research and potential applications of helminth EVs.

Ocean acidification can negatively affect a broad range of physiological processes in marine shelled molluscs. Marine bioeroding organisms could, in contrast, benefit from ocean acidification due to reduced energetic costs of bioerosion. Ocean acidification could thus exacerbate negative effects (e.g. reduced growth) of ocean acidification and shell borers on oysters. The aim of this study was to assess the impact of ocean acidification on the oyster Ostrea chilensis, the boring sponge Cliona sp., and their host-parasite relationship. We exposed three sets of organisms 1) O. chilensis, 2) Cliona sp., and 3) O. chilensis infested with Cliona sp. to pHT 8.03, 7.83, and 7.63. Reduced pH had no significant effect on calcification, respiration and clearance rate of uninfested O. chilensis. Low pH significantly reduced calcification leading to net dissolution of oyster shells at pHT 7.63 in sponge infested oysters. Net dissolution was likely caused by increased bioerosion by Cliona sp. at pHT 7.63. Additionally, declining pH and sponge infestation had a significant negative antagonistic effect (less negative than predicted additively) on clearance rate. This interaction suggests that sponge infested oysters increase clearance rates to cope with higher energy demand of increased shell repair resulting from higher boring activity of Cliona sp. at low seawater pH. O. chilensis body condition was unaffected by sponge infestation, pH, and the interaction of the two. The reduction in calcification rate suggests sponge infestation and ocean acidification together would exacerbate direct (reduced growth) and indirect (e.g., increased predation) negative effects on oyster health and survival. Our results indicate that ocean acidification by the end of the century could have severe consequences for marine molluscs with boring organisms.

Abstract Background The role of pathogen genotype in determining disease severity and immunopathology has been studied intensively in microbial pathogens including bacteria, fungi, protozoa and viruses but is poorly understood in parasitic helminths. The medically important blood fluke Schistosoma mansoni is an excellent model system to study the impact of helminth genetic variation on immunopathology. Our laboratory has demonstrated that laboratory schistosome populations differ in sporocyst growth and cercarial production in the intermediate snail host and worm establishment and fecundity in the vertebrate host. Here, we (i) investigate the hypothesis that schistosome genotype plays a significant role in immunopathology and related parasite life history traits in the vertebrate mouse host and (ii) quantify the relative impact of parasite and host genetics on infection outcomes. Methods We infected BALB/c and C57BL/6 mice with four different laboratory schistosome populations from Africa and the Americas. We quantified disease progression in the vertebrate host by measuring body weight and complete blood count (CBC) with differential over a 12-week infection period. On sacrifice, we assessed parasitological (egg and worm counts, fecundity), immunopathological (organ measurements and histopathology) and immunological (CBC with differential and cytokine profiles) characteristics to determine the impact of parasite and host genetics. Results We found significant variation between parasite populations in worm numbers, fecundity, liver and intestine egg counts, liver and spleen weight, and fibrotic area but not in granuloma size. Variation in organ weight was explained by egg burden and intrinsic parasite factors independent of egg burden. We found significant variation between infected mouse lines in cytokine levels (IFN-γ, TNF-α), eosinophils, lymphocytes and monocyte counts. Conclusions This study showed that both parasite and host genotype impact the outcome of infection. While host genotype explains most of the variation in immunological traits, parasite genotype explains most of the variation in parasitological traits, and both host and parasite genotypes impact immunopathology outcomes. Graphical Abstract

Abstract Background Many parasitic plants of the genera Striga and Cuscuta inflict huge agricultural damage worldwide. To form and maintain a connection with a host plant, parasitic plants deploy virulence factors (VFs) that interact with host biology. They possess a secretome that represents the complement of proteins secreted from cells and like other plant parasites such as fungi, bacteria or nematodes, some secreted proteins represent VFs crucial to successful host colonisation. Understanding the genome-wide complement of putative secreted proteins from parasitic plants, and their expression during host invasion, will advance understanding of virulence mechanisms used by parasitic plants to suppress/evade host immune responses and to establish and maintain a parasite-host interaction. Results We conducted a comparative analysis of the secretomes of root (Striga spp.) and shoot (Cuscuta spp.) parasitic plants, to enable prediction of candidate VFs. Using orthogroup clustering and protein domain analyses we identified gene families/functional annotations common to both Striga and Cuscuta species that were not present in their closest non-parasitic relatives (e.g. strictosidine synthase like enzymes), or specific to either the Striga or Cuscuta secretomes. For example, Striga secretomes were strongly associated with ‘PAR1’ protein domains. These were rare in the Cuscuta secretomes but an abundance of ‘GMC oxidoreductase’ domains were found, that were not present in the Striga secretomes. We then conducted transcriptional profiling of genes encoding putatively secreted proteins for the most agriculturally damaging root parasitic weed of cereals, S. hermonthica. A significant portion of the Striga-specific secretome set was differentially expressed during parasitism, which we probed further to identify genes following a ‘wave-like’ expression pattern peaking in the early penetration stage of infection. We identified 39 genes encoding putative VFs with functions such as cell wall modification, immune suppression, protease, kinase, or peroxidase activities, that are excellent candidates for future functional studies. Conclusions Our study represents a comprehensive secretome analysis among parasitic plants and revealed both similarities and differences in candidate VFs between Striga and Cuscuta species. This knowledge is crucial for the development of new management strategies and delaying the evolution of virulence in parasitic weeds.

Abstract Background The Argentine stem weevil (ASW, Listronotus bonariensis) is a significant pasture pest in Aotearoa New Zealand, primarily controlled by the parasitoid biocontrol agent Microctonus hyperodae. Despite providing effective control of ASW soon after release, M. hyperodae parasitism rates have since declined significantly, with ASW hypothesised to have evolved resistance to its biocontrol agent. While the parasitism arsenal of M. hyperodae has previously been investigated, revealing many venom components and an exogenous novel DNA virus Microctonus hyperodae filamentous virus (MhFV), the effects of said arsenal on gene expression in ASW during parasitism have not been examined. In this study, we performed a multi-species transcriptomic analysis to investigate the biology of ASW parasitism by M. hyperodae, as well as the decline in efficacy of this biocontrol system. Results The transcriptomic response of ASW to parasitism by M. hyperodae involves modulation of the weevil’s innate immune system, flight muscle components, and lipid and glucose metabolism. The multispecies approach also revealed continued expression of venom components in parasitised ASW, as well as the transmission of MhFV to weevils during parasitism and some interrupted parasitism attempts. Transcriptomics did not detect a clear indication of parasitoid avoidance or other mechanisms to explain biocontrol decline. Conclusions This study has expanded our understanding of interactions between M. hyperodae and ASW in a biocontrol system of critical importance to Aotearoa-New Zealand’s agricultural economy. Transmission of MhFV to ASW during successful and interrupted parasitism attempts may link to a premature mortality phenomenon in ASW, hypothesised to be a result of a toxin-antitoxin system. Further research into MhFV and its potential role in ASW premature mortality is required to explore whether manipulation of this viral infection has the potential to increase biocontrol efficacy in future.

The present research highlights the critical importance of understanding S. mansoni infection in global public health. Using a network-based pharmacological approach, this study explores parasite biology, disease mechanisms, and potential treatments. Praziquantel and its derivatives are identified as key drugs for treating schistosomiasis. ADMET and molecular docking predict the preferred binding orientation of drug candidates, like Mol4, with target proteins. Analyzing network pharmacology, disease classification, enrichment studies, and pathways reveals the biological processes influenced by these candidates. The research emphasizes the need for comprehensive healthcare in endemic regions and identifies critical pathways and target proteins, such as zinc-binding proteins and endopeptidases, as promising drug targets. The integration of molecular docking and network pharmacology provides a strong platform for advancing drug development and devising effective treatment strategies against this debilitating parasitic infection, ultimately contributing to the enhancement of global public health.

Background: The role of pathogen genotype in determining disease severity and immunopathology has been studied intensively in microbial pathogens including bacteria, fungi, protozoa and viruses but is poorly understood in parasitic helminths. The medically important blood fluke Schistosoma mansoni is an excellent model system to study the impact of helminth genetic variation on immunopathology. Our laboratory has demonstrated that laboratory schistosome populations differ in sporocyst growth and cercarial production in the intermediate snail host and worm establishment and fecundity in the vertebrate host. Here, we (i) investigate the hypothesis that schistosome genotype plays a significant role in immunopathology and related parasite life history traits in the vertebrate mouse host and (ii) quantify the relative impact of parasite and host genetics on infection outcomes. Methods: We infected BALB/c and C57BL/6 mice with four different laboratory schistosome populations from Africa and the Americas. We quantified disease progression in the vertebrate host by measuring body weight and complete blood count (CBC) with differential over a 12-week infection period. On sacrifice, we assessed parasitological (egg and worm counts, fecundity), immunopathological (organ measurements and histopathology) and immunological (CBC with differential and cytokine profiles) characteristics to determine the impact of parasite and host genetics. Results: We found significant variation between parasite populations in worm numbers, fecundity, liver and intestine egg counts, liver and spleen weight, and fibrotic area but not in granuloma size. Variation in organ weight was explained by egg burden and intrinsic parasite factors independent of egg burden. We found significant variation between infected mouse lines in cytokine levels (IFN-γ, TNF-α), eosinophils, lymphocytes and monocyte counts. Conclusions: This study showed that both parasite and host genotype impact the outcome of infection. While host genotype explains most of the variation in immunological traits, parasite genotype explains most of the variation in parasitological traits, and both host and parasite genotypes impact immunopathology outcomes. [ABSTRACT FROM AUTHOR]

Observations of Black Spot Syndrome (BSS), a pigmented dermatopathy in marine fishes, have been increasingly reported in important grazers such as surgeonfish and parrotfish in the Caribbean. This condition has been linked to infection by the trematode parasite, Scaphanocephalus spp., although relatively little is known about the environmental drivers of infection and how they vary spatially. This study introduces a non-invasive, video-based method to survey BSS presence and severity in ocean surgeonfish (Acanthurus tractus). Application of the approach across 35 coastal sites in Curaçao was used to evaluate the influence of environmental factors on BSS, including longitude, herbivorous fish density, wave energy, depth, nutrient pollution, and inhabited surface area. Of the 5123 fish surveyed between February 2022 and January 2023, 70% exhibited visible signs of BSS, and the average number of lesions per fish increased by ~ fivefold from eastern to western sites along the leeward coastline. Within a site, estimates of BSS severity were broadly consistent between different divers, different reviewers of video footage, and the date of sampling, emphasizing the robustness of the surveillance approach. Analyses of environmental factors indicated that BSS decreased with wave intensity while increasing in association with higher nutrient runoff and fishing pressure. This study provides insight into environmental correlates of BSS severity while highlighting the use of video-based surveillance as a non-invasive survey method. The mechanisms linking environmental factors with BSS as well as its consequences for affected fish remain unknown, emphasizing the need for long-term and experimental studies in this system. [ABSTRACT FROM AUTHOR]

Purpose: During malarial infection, both parasites and host red blood cells (RBCs) come under severe oxidative stress due to the production of free radicals. The host system responds in protecting the RBCs against the oxidative damage caused by these free radicals by producing antioxidants. In this study, we investigated the antioxidant enzyme; superoxide dismutase (SOD) activity and cytokine interactions with parasitaemia in Ghanaian children with severe and uncomplicated malaria. Methodology: One hundred and fifty participants aged 0–12 years were administered with structured questionnaires. Active case finding approach was used in participating hospitals to identify and interview cases before treatment was applied. Blood samples were taken from each participant and used to quantify malaria parasitaemia, measure haematological parameters and SOD activity. Cytokine levels were measured by commercial ELISA kits. DNA comet assay was used to evaluate the extent of parasite DNA damage due to oxidative stress. Results: Seventy – Nine (79) and Twenty- Six (26) participants who were positive with malaria parasites were categorized as severe (56.75 × 103 ± 57.69 parasites/µl) and uncomplicated malaria (5.87 × 103 ± 2.87 parasites/µl) respectively, showing significant difference in parasitaemia (p < 0.0001). Significant negative correlation was found between parasitaemia and SOD activity levels among severe malaria study participants (p = 0.0428). Difference in cytokine levels (IL-10) amongst the control, uncomplicated and severe malaria groups was significant (p < 0.0001). The IFN-γ/IL-10 /TNF-α/IL-10 ratio differed significantly between the malaria infected and non- malaria infected study participants. DNA comet assay revealed damage to Plasmodium parasite DNA. Conclusion: Critical roles played by SOD activity and cytokines as anti-parasitic defense during P. falciparum malaria infection in children were established. [ABSTRACT FROM AUTHOR]

We investigated organ specific Toxocara canis larval migration in mice infected with T. canis larvae. We observed the worm burden and systemic immune responses. Three groups of BALB/c mice (n=5 each) were orally administered 1,000 T. canis 2nd stage larvae to induce larva migrans. Mice were sacrificed at 1, 3, and 5 weeks post-infection. Liver, lung, brain, and eye tissues were collected. Tissue from 2 mice per group was digested for larval count, while the remaining 3 mice underwent histological analysis. Blood hematology and serology were evaluated and compared to that in a control uninfected group (n=5) to assess the immune response. Cytokine levels in bronchoalveolar lavage (BAL) fluid were also analyzed. We found that, 1 week post-infection, the mean parasite load in the liver (72±7.1), brain (31±4.2), lungs (20±5.7), and eyes (2±0) peaked and stayed constant until the 3 weeks. By 5-week post-infection, the worm burden in the liver and lungs significantly decreased to 10±4.2 and 9±5.7, respectively, while they remained relatively stable in the brain and eyes (18±4.2 and 1±0, respectively). Interestingly, ocular larvae resided in all retinal layers, without notable inflammation in outer retina. Mice infected with T. canis exhibited elevated levels of neutrophils, monocytes, eosinophils, and immunoglobulin E. At 5 weeks post-infection, interleukin (IL)-5 and IL-13 levels were elevated in BAL fluid. Whereas IL-4, IL-10, IL-17, and interferon-γ levels in BAL fluid were similar to that in controls. Our findings demonstrate that a small portion of T. canis larvae migrate to the eyes and brain within the first week of infection. Minimal tissue inflammation was observed, probably due to increase of anti-inflammatory cytokines. This study contributes to our understanding of the histological and immunological responses to T. canis infection in mice, which may have implications to further understand human toxocariasis. [ABSTRACT FROM AUTHOR]

Background: Many parasitic plants of the genera Striga and Cuscuta inflict huge agricultural damage worldwide. To form and maintain a connection with a host plant, parasitic plants deploy virulence factors (VFs) that interact with host biology. They possess a secretome that represents the complement of proteins secreted from cells and like other plant parasites such as fungi, bacteria or nematodes, some secreted proteins represent VFs crucial to successful host colonisation. Understanding the genome-wide complement of putative secreted proteins from parasitic plants, and their expression during host invasion, will advance understanding of virulence mechanisms used by parasitic plants to suppress/evade host immune responses and to establish and maintain a parasite-host interaction. Results: We conducted a comparative analysis of the secretomes of root (Striga spp.) and shoot (Cuscuta spp.) parasitic plants, to enable prediction of candidate VFs. Using orthogroup clustering and protein domain analyses we identified gene families/functional annotations common to both Striga and Cuscuta species that were not present in their closest non-parasitic relatives (e.g. strictosidine synthase like enzymes), or specific to either the Striga or Cuscuta secretomes. For example, Striga secretomes were strongly associated with 'PAR1' protein domains. These were rare in the Cuscuta secretomes but an abundance of 'GMC oxidoreductase' domains were found, that were not present in the Striga secretomes. We then conducted transcriptional profiling of genes encoding putatively secreted proteins for the most agriculturally damaging root parasitic weed of cereals, S. hermonthica. A significant portion of the Striga-specific secretome set was differentially expressed during parasitism, which we probed further to identify genes following a 'wave-like' expression pattern peaking in the early penetration stage of infection. We identified 39 genes encoding putative VFs with functions such as cell wall modification, immune suppression, protease, kinase, or peroxidase activities, that are excellent candidates for future functional studies. Conclusions: Our study represents a comprehensive secretome analysis among parasitic plants and revealed both similarities and differences in candidate VFs between Striga and Cuscuta species. This knowledge is crucial for the development of new management strategies and delaying the evolution of virulence in parasitic weeds. [ABSTRACT FROM AUTHOR]

Insects have become exciting model organisms for studying animal medication due to their comparative ease of rearing and experimental manipulation, short generation times, and diverse levels of sociality. Adopting an inclusive fitness framework has revealed the importance of medication for maximizing both direct and indirect fitness. Historically, medication research focused on chemicals or behaviors directly toxic to parasites. Recent studies have investigated how animal medication modulates the host immune system, revealing limited evidence of a strong role. Insect studies have led the way in showing that nutrients and toxins can alter animal microbiomes and thereby modulate disease resistance. A better understanding of the ecological interactions between insects and their natural enemies and environment will help to establish the relative costs and benefits of animal medication. Like humans, animals use plants and other materials as medication against parasites. Recent decades have shown that the study of insects can greatly advance our understanding of medication behaviors. The ease of rearing insects under laboratory conditions has enabled controlled experiments to test critical hypotheses, while their spectrum of reproductive strategies and living arrangements – ranging from solitary to eusocial communities – has revealed that medication behaviors can evolve to maximize inclusive fitness through both direct and indirect fitness benefits. Studying insects has also demonstrated in some cases that medication can act through modulation of the host's innate immune system and microbiome. We highlight outstanding questions, focusing on costs and benefits in the context of inclusive host fitness. [ABSTRACT FROM AUTHOR]

Gastrointestinal nematode (GIN) infection has applied significant evolutionary pressure to the mammalian immune system and remains a global economic and human health burden. Upon infection, type 2 immune sentinels activate a common antihelminth response that mobilizes and remodels the intestinal tissue for effector function; however, there is growing appreciation of the impact GIN infection also has on the distal tissue immune state. Indeed, this effect is observed even in tissues through which GINs never transit. This review highlights how GIN infection modulates systemic immunity through (a) induction of host resistance and tolerance responses, (b) secretion of immunomodulatory products, and (c) interaction with the intestinal microbiome. It also discusses the direct consequences that changes to distal tissue immunity can have for concurrent and subsequent infection, chronic noncommunicable diseases, and vaccination efficacy. [ABSTRACT FROM AUTHOR]

Background: The Argentine stem weevil (ASW, Listronotus bonariensis) is a significant pasture pest in Aotearoa New Zealand, primarily controlled by the parasitoid biocontrol agent Microctonus hyperodae. Despite providing effective control of ASW soon after release, M. hyperodae parasitism rates have since declined significantly, with ASW hypothesised to have evolved resistance to its biocontrol agent. While the parasitism arsenal of M. hyperodae has previously been investigated, revealing many venom components and an exogenous novel DNA virus Microctonus hyperodae filamentous virus (MhFV), the effects of said arsenal on gene expression in ASW during parasitism have not been examined. In this study, we performed a multi-species transcriptomic analysis to investigate the biology of ASW parasitism by M. hyperodae, as well as the decline in efficacy of this biocontrol system. Results: The transcriptomic response of ASW to parasitism by M. hyperodae involves modulation of the weevil's innate immune system, flight muscle components, and lipid and glucose metabolism. The multispecies approach also revealed continued expression of venom components in parasitised ASW, as well as the transmission of MhFV to weevils during parasitism and some interrupted parasitism attempts. Transcriptomics did not detect a clear indication of parasitoid avoidance or other mechanisms to explain biocontrol decline. Conclusions: This study has expanded our understanding of interactions between M. hyperodae and ASW in a biocontrol system of critical importance to Aotearoa-New Zealand's agricultural economy. Transmission of MhFV to ASW during successful and interrupted parasitism attempts may link to a premature mortality phenomenon in ASW, hypothesised to be a result of a toxin-antitoxin system. Further research into MhFV and its potential role in ASW premature mortality is required to explore whether manipulation of this viral infection has the potential to increase biocontrol efficacy in future. [ABSTRACT FROM AUTHOR]

Simple Summary: The classical biological control approach is generally used in biological control practice. Through this research, we reveal the findings of a new association between S. frugiperda, an invasive corn pest in several nations, including Indonesia, and local parasitoids, suggesting the new association approaches in biological control practices. Telenomus remus is the most dominant egg parasitoid of S. frugiperda found in the field, suggesting their quick adaptation to new pests. Spodopotera frugiperda is a worldwide invasive pest that has caused significant economic damage. According to the classical biological control approach, natural enemies that can control invasive pests come from the same area of origin as the pests that have experienced coadaptation processes. However, the new association's approach suggests that local natural enemies are equally capable of controlling invasive pests. Due to the lack of data on the association of S. frugiperda and local natural enemies, research was conducted through a rapid survey to study the diversity of parasitoids associated with S. frugiperda. The results showed 15 parasitoid species associated with S. frugiperda. Four egg parasitoids, eight larval parasitoids, and three larval–pupal parasitoids were found to be associated with S. frugiperda for three years after it was first discovered in Indonesia. Eleven of them are new reports of parasitoids associated with S. frugiperda in Indonesia. A new association was found between S. frugiperda and twelve parasitoid species, consisting of three egg parasitoids (Platygasteridaesp.01, Platygasteridaesp.02, and Telenomus remus), six larval parasitoids (Apanteles sp., Microplitis sp., Campoletis sp., Coccygidium sp., Eupelmus sp., and Stenobracon sp.), and three larval–pupal parasitoids (Brachymeria lasus, B. femorata, and Charops sp.). Telenomus remus is the most dominant parasitoid, with a higher abundance and parasitism rate. The result suggests another method for selecting biological control using the new association approach since local natural enemies can foster quick adaptation to invasive pests. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) are regulatory transcripts during protozoan infections in the host intestinal epithelial cells (IECs). Apicomplexan Eimeria falciformis sporozoite extracellular vesicles (EVs) contain virulence factors that modulate host IECs pro‐inflammatory genes and immune responses. In this study, E. falciformis sporozoites were made to interact with inactivated host cells, and the parasite EVs were separated from total secretome by ultracentrifugation and purified on density gradient medium. Dose‐dependent bio‐activity of E. falciformis EVs was investigated by RNA sequencing, functional annotation and quantitative PCR. It was found that E. falciformis EVs induced mRNA, circRNA, and lncRNA expressions in mouse IECs. Of 38, 217 lncRNAs assembled, 157 and 152 were upwardly and downwardly expressed respectively. Differentially expressed lncRNAs were associated with cytokines, pyroptosis, and immune signaling pathways including FoxO, NF‐κB, MAPK, and TGF‐β. In essence, E. falciformis EVs altered host cell RNA expressions during the interaction with host IECs. Also, differentially expressed lncRNAs are potential diagnostic transcripts during Eimeria infections. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) have emerged as key intercellular communication and pathogenesis mediators. Parasitic organisms’ helminths, cause widespread infections with significant health impacts worldwide. Recent research has shed light on the role of EVs in the lifecycle, immune evasion, and disease progression of these parasitic organisms. These tiny membrane-bound organelles including microvesicles and exosomes, facilitate the transfer of proteins, lipids, mRNAs, and microRNAs between cells. EVs have been isolated from various bodily fluids, offering a potential diagnostic and therapeutic avenue for combating infectious agents. According to recent research, EVs from helminths hold great promise in the diagnosis of parasitic infections due to their specificity, early detection capabilities, accessibility, and the potential for staging and monitoring infections, promote intercellular communication, and are a viable therapeutic tool for the treatment of infectious agents. Exploring host-parasite interactions has identified promising new targets for diagnostic, therapy, and vaccine development against helminths. This literature review delves into EVS’s origin, nature, biogenesis, and composition in these parasitic organisms. It also highlights the proteins and miRNAs involved in EV release, providing a comprehensive summary of the latest findings on the significance of EVs in the biology of helminths, promising targets for therapeutic and diagnostic biomarkers.

The detection of severe limb malformations in metamorphosing northern leopard frogs (Rana pipiens) from a Colorado pond in August 2022 prompted questions about the cause(s) and concern over the implications. Northern leopard frogs, which are a Tier 1 Species of Greatest Conservation Need in Colorado, have declined over much of their range in the state, particularly along the Front Range. Although malformations in amphibians have been reported in other parts of the USA, they are rare in Colorado, and the current case represents the most severe hotspot reported in the state for over 70 years. Across three survey events in late summer and early fall of 2022, approximately 68% of captured leopard frogs (late-stage larvae and metamorphic frogs) exhibited one or more malformations. Malformations exclusively affected the hind limbs and were dominated by skin webbings (51.7% of the total), bony triangles (32.2%), and extra limbs or digits (11%). Many animals had multiple malformations that limited the movement of one or both limbs (average of 2.3 malformations per malformed frog). Dissection of a subset of animals coupled with 28S rDNA genetic sequencing revealed the occurrence of the trematode Ribeiroia ondatrae at an average of 75.2 trematode cysts (metacercariae) per frog. The parasite was also detected in 2.6% of dissected snails (Helisoma trivolvis), which function as the trematode's first intermediate host. The relatively high loads of infection detected here – coupled with the similarity of observed malformations to those previously linked to R. ondatrae in experimental studies and from other malformation hotspots in the USA – offer compelling evidence that the current case is the result of parasite infection. Unresolved questions include why malformation prevalence was so high in 2022 and the degree to which such abnormalities will affect population persistence for local leopard frogs, particularly if malformations continue.

Abstract Schistosomiasis is a neglected tropical disease that affects humans and animals in tropical and subtropical regions worldwide. Schistosome eggs are responsible for the pathogenesis and transmission of schistosomiasis, thus reducing egg production is vital for prevention and control of schistosomiasis. However, the mechanisms underlying schistosome reproduction remain unclear. Annexin proteins (ANXs) are involved in the physiological and pathological functions of schistosomes, but the specific regulatory mechanisms and roles of ANX A13 in the development of Schistosoma japonicum and host–parasite interactions remain poorly understood. Therefore, in this study, the expression profiles of SjANX A13 at different life cycle stages of S. japonicum were assessed using quantitative PCR. In addition, the expression profiles of the homolog in S. mansoni were analyzed in reference to public datasets. The results of RNA interference showed that knockdown of SjANX A13 significantly affected the development and egg production of female worms in vivo. The results of an immune protection assay showed that recombinant SjANX A13 increased production of immunoglobulin G-specific antibodies. Finally, co-culture of S. japonicum exosomes with LX-2 cells using a transwell system demonstrated that SjANX A13 is involved in host–parasite interactions via exosomes. Collectively, these results will help to clarify the roles of SjANX A13 in the development of S. japonicum and host–parasite interactions as a potential vaccine candidate.

Outbreaks of environmentally transmitted parasites require that susceptible hosts encounter transmission stages in the environment and become infected, but we also know that transmission stages can be in the environment without triggering disease outbreaks. One challenge in understanding the relationship between environmental transmission stages and disease outbreaks is that the distribution and abundance of transmission stages outside of their hosts have been difficult to quantify. Thus, we have limited data about how changes in transmission stage abundance influence disease dynamics; moreover, we do not know whether the relationship between transmission stages and outbreaks differs among parasite species. We used digital PCR to quantify the environmental transmission stages of five parasites in six lakes in southeastern Michigan every 2 weeks from June to November 2021. At the same time, we quantified infection prevalence in hosts and host density. Our study focused on eight zooplankton host species (Daphnia spp. and Ceriodaphnia dubia) and five of their parasites from diverse taxonomic groups (bacteria, yeast, microsporidia, and oomycete) with different infection mechanisms. We found that parasite transmission stage concentration increased prior to disease outbreaks for all parasites. However, parasites differed significantly in the relative timing of peaks in transmission stage concentration and infection outbreaks. The "continuous shedder" parasites had transmission stage peaks at the same time as or slightly after the outbreak peaks. In contrast, parasites relying on host death for transmission ("obligate killers") had transmission stage peaks before outbreak peaks. For most parasites, lakes with outbreaks had higher spore concentrations than those without outbreaks, especially once an outbreak began; the exception was for a parasite, Pasteuria ramosa, with very strong genotypic specificity of infection. Overall, our results show that disease outbreaks are tightly linked to transmission stage concentration; outbreaks were preceded by increases in transmission stage concentration in the environment and then were fueled by the production of more transmission stages during the outbreak itself, with concentrations decreasing to pre‐outbreak levels as outbreaks waned. Thus, tracking transmission stages in the environment improves our understanding of the drivers of disease outbreaks and reveals how parasite traits may affect these dynamics. [ABSTRACT FROM AUTHOR]

Toxoplasmosis, caused by the protozoan Toxoplasma gondii, is the zoonosis widespread all over the world. Birds constitute an important group of T. gondii intermediate hosts often attacked by definitive hosts, e.g. domestic cats. Due to confirmation of an additional way of T. gondii transmission via tick bite, the aim of our study was to state and evaluate the infection prevalence of ticks feeding on blackbirds (Turdus merula) and song thrushes (Turdus philomelos). The real-time PCR amplification of the B1 gene fragment was used for detection of T. gondii infection in 157 Ixodes ricinus ticks removed from captured birds. The results showed the thrushes as hosts intensively attacked by ticks (prevalence 88.5% and 70% for blackbirds and song thrushes, respectively), and T. gondii infected individuals were detected. Among all ticks infected, 7 (5.8%; n = 120) were collected from blackbirds, and 2 (5.4%; n = 37) from song thrushes. The thrushes small body sizes and their tendency to urban ecosystems colonization, suggest that they relatively often become a pray of domestic cats, and combined with our findings, are potentially involved in maintenance the T. gondii population, especially in anthropogenic habitats, where the presence of toxoplasmosis is likely to constitute a serious danger to public health. [ABSTRACT FROM AUTHOR]

Cutaneous leishmaniasis, a parasitic disease caused by Leishmania major, is a widely frequent form in humans. To explore the importance of the host gut microbiota and to investigate its changes during L. major infection, two different groups of mouse models were assessed. The microbiome of two parts of the host gut—ileum and colon—from infected and non-infected mice were characterised by sequencing of 16S rDNA using an Ion Torrent PGM platform. Microbiome analysis was performed to reveal changes related to the susceptibility and the genetics of mice strains in two different gut compartments and to compare the results between infected and non-infected mice. The results showed that Leishmania infection affects mainly the ileum microbiota, whereas the colon bacterial community was more stable. Different biomarkers were determined in the gut microbiota of infected resistant mice and infected susceptible mice using LEfSe analysis. Lactobacillaceae was associated with resistance in the colon microbiota of all resistant mice strains infected with L. major. Genes related to xenobiotic biodegradation and metabolism and amino acid metabolism were primarily enriched in the small intestine microbiome of resistant strains, while genes associated with carbohydrate metabolism and glycan biosynthesis and metabolism were most abundant in the gut microbiome of the infected susceptible mice. These results should improve our understanding of host-parasite interaction and provide important insights into the effect of leishmaniasis on the gut microbiota. Also, this study highlights the role of host genetic variation in shaping the diversity and composition of the gut microbiome. Key points: • Leishmaniasis may affect mainly the ileum microbiota while colon microbiota was more stable. • Biomarkers related with resistance or susceptibility were determined in the gut microbiota of mice. • Several pathways were predicted to be upregulated in the gut microbiota of resistant or susceptible mice. [ABSTRACT FROM AUTHOR]

Despite the importance of virulence in epidemiological theory, the relative contributions of host and parasite to virulence outcomes remain poorly understood. Here, we use reciprocal cross experiments to disentangle the influence of host and parasite on core virulence components—infection and pathology—and understand dramatic differences in parasite‐induced malformations in California amphibians. Surveys across 319 populations revealed that amphibians' malformation risk was 2.7× greater in low‐elevation ponds, even while controlling for trematode infection load. Factorial experiments revealed that parasites from low‐elevation sites induced higher per‐parasite pathology (reduced host survival and growth), whereas there were no effects of host source on resistance or tolerance. Parasite populations also exhibited marked differences in within‐host distribution: ~90% of low‐elevation cysts aggregated around the hind limbs, relative to <60% from high‐elevation. This offers a novel, mechanistic basis for regional variation in parasite‐induced malformations while promoting a framework for partitioning host and parasite contributions to virulence. [ABSTRACT FROM AUTHOR]

Chagas disease, endemic from Latin America, is caused by Trypanosoma cruzi and is transmitted by triatomine feces. This parasite undergoes complex morphological changes through its life cycle, promoted by significant changes in signal transduction pathways. The activity of protein kinase CK2 has been described in trypanosomatids. Using a specific peptide and radioactive ATP, we identified CK2 activity on the cellular surface and the cytoplasmic content in Trypanosoma cruzi, apart from the secreted form. Dephosphorylated casein promoted an increase of 48% in the secreted CK2 activity. Total extract of peritoneal macrophages from BALB/c and inactivated human serum promoted an increase of 67% and 36%, respectively, in this activity. The protein secreted by parasites was purified by HPLC and had shown compatibility with the catalytic subunit of mammalian CK2. Incubation of the parasites with CK2 inhibitors, added to the culture medium, prevented their growth. The opposite was observed when CK2 activators were used. Results of interaction between Trypanosoma cruzi and the gut of the vector have revealed that, in the presence of CK2 inhibitors, there is a reduction in the association rate. A similar inhibition profile was seen in the Trypanosoma cruzi-macrophages interaction, confirming the importance of this enzyme in the life cycle of this protozoan. [ABSTRACT FROM AUTHOR]

Mesanophrys sp. is a parasitic ciliate that invades and destroys the hemocytes of the swimming crab (Portunus trituberculatus). In the present study, we employed an in vitro model to elucidate how Mesanophrys sp. destroys crab hemocytes. We also evaluated the relationship between the parasite’s density, the destruction rate of the hemocytes, and the rapid proliferation pattern of parasites in host crabs. We found that the survival rate and cell integrity of crab hemocytes decreased with an increase in Mesanophrys sp. density, depicting a negative correlation between hemocyte viability and parasite density. Further analyses revealed that crab hemocytes could resist destruction by a low density (10 ind/mL) of Mesanophrys sp. for a long time (60 h). Mesanophrys sp. and its culture medium (containing the ciliate secretions) destroy the host hemocytes. The natural population growth rate of Mesanophrys sp. decreased with an increase in the parasite density, but the Mesanophrys sp. density did not affect the generation time of the parasites. In summary, Mesanophrys sp. can destroy crab hemocytes, and the degree of destruction is directly proportional to the parasite density. The resistance of crab hemocytes to Mesanophrys sp. decreased gradually with an increase in the parasite density. [ABSTRACT FROM AUTHOR]