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Treponema denticola, a bacterium that forms a "red complex" with Porphyromonas gingivalis and Tannerella forsythia, is associated with periodontitis, pulpitis, and other oral infections. The major surface protein (Msp) is a surface glycoprotein with a relatively well-established overall domain structure (N-terminal, central and C-terminal regions) and a controversial tertiary structure. As one of the key virulence factors of T. denticola, Msp is associated with adherence, immune response, and pore formation by the microorganism. It also mediates several pathological changes in histocytes, such as cytoskeleton disruption, neutrophil phagocytosis, and phosphoinositide balance interruption. In addition, the Msp of T. denticola is also an ortholog of the Treponema pallidum repeat (Tpr) proteins and Msp or Msp-like proteins that have been detected in other oral treponeme species. This review will discuss the structure, pathogenicity and homologs of Msp produced by T. denticola, illuminate the controversy regarding the structure and membrane topology of native Msp, explore the potential roles of Msp in the mechanism of T. denticola immune escape and provide an overview of the cytotoxicity and adherence ability of Msp. Further understanding of the structure and functions of Msp will offer new insights that will help promote further investigations of the pathogenic mechanisms of T. denticola and other treponemes, leading to more effective prophylactic or therapeutic treatments for relevant diseases., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Parasitism as a life strategy has independently evolved multiple times within the eukaryotic tree of life. Each lineage has developed mechanisms to invade hosts, exploit resources, and ensure replication, but our knowledge of survival mechanisms in many parasitic taxa remain extremely limited. One such group is the Myxozoa, which are obligate, dixenous cnidarians. Evidence suggests that myxozoans evolved from free-living ancestors to endoparasites around 600 million years ago and are likely one of the first metazoan parasites on Earth. Some myxozoans pose significant threats to farmed and wild fish populations, negatively impacting aquaculture and fish stocks; one such example is Sphaerospora molnari, which forms spores in the gills of common carp (Cyprinus carpio), disrupting gill epithelia and causing somatic and respiratory failure. Sphaerospora molnari undergoes sequential development in different organs of its host, with large numbers of morphologically distinct stages occurring in the blood, liver, and gills of carp. We hypothesize that these parasite life-stages differ in regards to their host exploitation, pathogenicity, and host immune evasion strategies and mechanisms. We performed stage-specific transcriptomic profiling to identify differentially expressed key functional gene groups that relate to these functions and provide a fundamental understanding of the mechanisms S. molnari uses to optimize its parasitic lifestyle. We aimed to identify genes that are likely related to parasite pathogenicity and host cell exploitation mechanisms, and we hypothesize that genes unique to S. molnari might be indicative of evolutionary innovations and specific adaptations to host environments. Results: We used parasite isolation protocols and comparative transcriptomics to study early proliferative and spore-forming stages of S. molnari, unveiling variation in gene expression between each stage. We discovered several apparent innovations in the S. molnari transcriptome, including proteins that are likely to function in the uptake of previously unknown key nutrients, immune evasion factors that may contribute to long-term survival in hosts, and proteins that likely improve adhesion to host cells that may have arisen from horizontal gene transfer. Notably, we identified genes that are similar to known virulence factors in other parasitic organisms, particularly blood and intestinal parasites like Plasmodium, Trypanosoma, and Giardia. Many of these genes are absent in published cnidarian and myxozoan datasets and appear to be specific to S. molnari; they may therefore represent potential innovations enabling Sphaerospora to exploit the host's blood system. Conclusions: In order to address the threat posed by myxozoans to both cultured fish species and wild stocks, it is imperative to deepen our understanding of their genetics. Sphaerospora molnari offers an appealing model for stage-specific transcriptomic profiling and for identifying differentially expressed key functional gene groups related to parasite development. We identified genes that are thus far unique to S. molnari, which reveal their evolutionary novelty and likely role as adaptations to specific host niches. In addition, we describe the pathogenicity-associated genetic toolbox of S. molnari and discuss the implications of our discoveries for disease control by shedding light on specific targets for potential intervention strategies. Highlights: We revealed Sphaerospora molnari developmental stage-specific expression profiles in infected host tissues. In gill stage parasites, genes related to development and cytoskeletal rearrangements are mostly up-regulated, while those up-regulated in the bloodstream stage are related to metabolism and host immune evasion strategies. We propose a list of "pathogenicity-related" gene families. We uncovered stage-specific up-regulation of S. molnari genes that have no homologues or were not found in other cnidarian lineages. [ABSTRACT FROM AUTHOR]

Animal husbandry development is influenced by various factors, with heat stress (HS) being a significant factor. The aim of this experiment was to explore the potential of natural antioxidants such as vitamin C (VITC), vitamin E (VITE), lycopene (LYC), and allicin (AL) in enhancing growth, immune function and maintaining the redox status of fattening rabbits under HS. Male weaning rabbits (n = 150, 5 weeks of age) were randomly assigned to 5 groups. The rabbits were fed a basal diet (control group) or supplemented with 40 mg of vitamin E (VE40), 5 mg of vitamin C (VC5), 150 mg of lycopene (LYC150), or 150 mg of allicin (AL150) per kg of diet, respectively, under summer Egyptian conditions. The overall temperature humidity index (THI) value was 29.76, indicating severe HS during the experimental period. The findings indicated that all dietary supplemented groups showed significant improvements in live body weight at 8 weeks (P < 0.0001) and 11 weeks (P < 0.05) of age compared to the control group. The feed conversion ratio (FCR) was improved with all additives (P < 0.05), while feed intake and carcass traits were not affected by the treatments (P > 0.05). The AL group had the highest dressing percentage compared to the other groups (P < 0.05). Feeding stressed rabbits with antioxidant supplements resulted in a higher hemoglobin concentration compared to the control group (P < 0.05). Aspartate transaminase (AST), triglycerides, and creatinine levels were decreased with all additives as compared to the control group (P < 0.05). Total protein and albumin were significantly higher in AL group than in other groups (P < 0.05). The serum Immunoglobulin G (IgG) was significantly increased, while tumor necrosis factor alpha (TNF-α), interleukin-4 (IL-4), and interferon gamma (IFN-γ) were decreased by all feed additives (P < 0.05). Immunoglobulins (IgA and IgM) did not differ among all experimental groups (P > 0.05). Serum total antioxidant capacity (TAC) and glutathione (GSH) levels were higher in all supplement groups compared to the HS group (P < 0.05). All dietary supplements significantly reduced malondialdehyde (MDA) levels in liver tissues and blood serum compared to the control group (P < 0.05). Collectively, allicin emerged as a potent shield against heat stress, bettering lycopene and vitamins E and C in safeguarding the well-being of growing rabbits. [ABSTRACT FROM AUTHOR]

Background: Treponemal diseases are a significant global health risk, presenting challenges to public health and severe consequences to individuals if left untreated. Despite numerous genomic studies on Treponema pallidum and the known possible biases introduced by the choice of the reference genome used for mapping, few investigations have addressed how these biases affect phylogenetic and evolutionary analysis of these bacteria. In this study, we ascertain the importance of selecting an appropriate genomic reference on phylogenetic and evolutionary analyses of T. pallidum. Results: We designed a multiple-reference-based (MRB) mapping strategy using four different reference genomes and compared it to traditional single-reference mapping. To conduct this comparison, we created a genomic dataset comprising 77 modern and ancient genomes from the three subspecies of T. pallidum, including a newly sequenced seventeenth century genome (35X mean coverage) of a syphilis-causing strain (designated as W86). Our findings show that recombination detection was consistent across different references, but the choice of reference significantly affected ancient genome reconstruction and phylogenetic inferences. The high-coverage W86 genome introduced in this study also provided a new calibration point for Bayesian molecular clock dating, improving the reconstruction of the evolutionary history of treponemal diseases. Additionally, we identified novel recombination events, positive selection targets, and refined dating estimates for key events in the species' history. Conclusions: This study highlights the importance of considering methodological implications and reference genome bias in high-throughput sequencing-based whole-genome analysis of T. pallidum, especially of ancient or low-coverage samples, contributing to a deeper understanding of the treponemal pathogen and its subspecies. [ABSTRACT FROM AUTHOR]

Hemolysin co-regulated protein 1 (Hcp1) is a component of the cluster 1 Type VI secretion system (T6SS1) that plays a key role during the intracellular lifecycle of Burkholderia pseudomallei. Hcp1 is recognized as a promising target antigen for developing melioidosis diagnostics and vaccines. While the gene encoding Hcp1 is retained across B. pseudomallei strains, variants of hcp1 have recently been identified. This study aimed to examine the prevalence of hcp1 variants in clinical isolates of B. pseudomallei, assess the antigenicity of the Hcp1 variants, and the ability of strains expressing these variants to stimulate multinucleated giant cell (MNGC) formation in comparison to strains expressing wild-type Hcp1 (Hcp1wt). Sequence analysis of 1,283 primary clinical isolates of B. pseudomallei demonstrated the presence of 8 hcp1 alleles encoding three types of Hcp1 proteins, including Hcp1wt (98.05%), Hcp1variant A (1.87%) and Hcp1variant B (0.08%). Compared to strains expressing Hcp1wt, those expressing the dominant variant, Hcp1variant A, stimulated lower levels of Hcp1variant A-specific antibody responses in melioidosis patients. Interestingly, when Hcp1variant A was expressed in B. pseudomallei K96243, this strain retained the ability to stimulate MNGC formation in A549 cells. In contrast, however, similar experiments with the Hcp1variant B demonstrated a decreased ability of B. pseudomallei to stimulate MNGC formation. Collectively, these results show that B. pseudomallei strains expressing variants of Hcp1 elicit variable antibody responses in melioidosis patients and differ in their ability to promote MNGC formation in cell culture. Author summary: Hcp1 is a component of the virulence-associated Type VI Secretion System 1 (T6SS1) that plays a significant role in the MNGC formation of B. pseudomallei in hosts. In addition to its importance in bacterial pathogenesis, Hcp1 is recognized by the host immune system, resulting in strong antigen-specific humoral and cellular responses in melioidosis patients and protective immunity in animal models. Our analysis of hcp1 sequences from 1,283 clinical B. pseudomallei isolates revealed genetic diversity and identified 8 hcp1 alleles and 3 types of Hcp1. We demonstrated that Hcp1variant A, associated with several amino acid changes, could still function in cell-to-cell spread similar to Hcp1wt, but it exhibited decreased specific antibody levels in plasma of melioidosis patients compared to the levels stimulated by Hcp1wt. Understanding the impact of possible antigenic variation with respect to immune responses and bacterial pathogenesis will be necessary to determine if expression of different Hcp1 proteins may have implications for the development of effective treatments and vaccines. [ABSTRACT FROM AUTHOR]

Purpose of Review: Antimicrobial resistance in sexually transmitted infections (STIs) has become an urgent global public health threat, raising the specter of untreatable infections. This review summarizes the determinants of resistance among the five most common curable STIs Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Treponema pallidum, and Trichomonas vaginalis, as well as strategies to mitigate the spread of resistance., Recent Findings: Genetic mutations are key drivers of resistance for N. gonorrhoeae and M. genitalium. Resistance in T. vaginalis can also occur because of genetic mutations, yet differential regulation of genes critical in antibiotic metabolism as well as co-infection with organisms that inactivate therapy play important roles. While resistance in C. trachomatis and T. pallidum has not been a substantial clinical concern, resistance selection via the continued widespread use of antimicrobials remains possible. While resistance determinants are diverse and differ by pathogen, the strategies required to mitigate the continued emergence of resistance are similar: prevention of infection and treatment diversification. Underpinning those strategies, surveillance remains essential for monitoring and responding to the threat of drug-resistant infections., Competing Interests: Declarations. Competing interests: C.S.B. and S.P. have received funds from SpeeDx Inc., to study resistance-guided therapy. C.A.M has received grants to her institution from Abbott, BioNTech, Gilead, Lupin, and Visby. She also reports honorarium and/or consulting fees from Cepheid, BioNTech, bioMérieux, Visby, Elsevier, Merck Manuals, UpToDate, and Abbott. S.J.J. has received consulting fees from Preventx Inc. L.A.B. has received honorarium from Elsevier and UpToDate. The remaining authors have no conflicts of interest to disclose., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)