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Plants respond to biotic stressors by modulating various processes in an attempt to limit the attack by a pathogen or herbivore. Triggering these different defense processes requires orchestration of a network of proteins and RNA molecules that includes microRNAs (miRNAs). These short RNA molecules (20–22 nucleotides) have been shown to be important players in the early responses of plants to stresses because they can rapidly regulate the expression levels of a network of downstream genes. The ascomycete Fusarium graminearum is an important fungal pathogen that causes significant losses in cereal crops worldwide. Using the well-characterized Fusarium-Arabidopsis pathosystem, we investigated how plants change expression of their miRNAs globally during the early stages of infection by F. graminearum. We have created a catalog of miRNAs that have differential expression in infected samples even before any visual symptoms of the infection are present. In addition to miRNAs that have been previously implicated in stress responses, we have also identified evolutionarily young miRNAs whose levels change significantly in response to fungal infection. Some of these young miRNAs have homologs present in cereals, which suggest that some of these miRNAs could be drivers of stress response. By examining if the miRNAs in this catalog have causal roles in plant infection response, a unique path toward development of plants with increased resistance to fungal pathogens can be developed. [ABSTRACT FROM AUTHOR]

Septoria tritici blotch (STB) is a devastating fungal disease affecting durum and bread wheat worldwide. Tunisian durum wheat landraces are reported to be valuable genetic resources for resistance to STB and should prominently be deployed in breeding programs to develop new varieties resistant to STB disease. In this study, a collection of 367 old durum and 6 modern wheat genotypes previously assessed using single Tunisian Zymoseptoria tritici isolate TUN06 during 2016 and 2017 and TM220 isolate during 2017 were phenotyped for resistance to a mixture of isolates (BULK) under field conditions. Significant correlations for disease traits using the three different inoculums were observed. Using 7638 SNP markers, fifty-one marker-trait associations (MTAs) for STB resistance were identified by genome-wide association study (GWAS) at Bonferroni correction threshold of -log10(P) > 5.184 with phenotypic variance explained (PVE) reaching up to 58%. A total of eleven QTL were identified using TUN06 isolate mean disease scoring (TUNMeanD and TUNMeanA) including threeQTL controlling resistance to both isolates TUN06 and TM220. A major QTL was identified on each of chromosomes 1B, 4B, 5A, and 7B, respectively. The QTL on 7B chromosome colocalized with Stb8 identified in bread wheat. Four QTL including the major QTL identified on chromosome 1B were considered as novel. SNP linked to the significant QTL have the potential to be used in marker-assisted selection for breeding for resistance to STB. [ABSTRACT FROM AUTHOR]

Objective: Black wool can effectively prevent sheep from DNA damage as well as fungal infection, and can improve reproductive performance. In order to explore the candidate genes related to black wool formation in Qira sheep. Methods: We selected 123 adult healthy ewes with different coat colors in Qira sheep groups (black (B), brown (Y) and grey (G)) and extracted DNA from their venous blood to obtain Illumina Ovine SNP 50K chip data. Subsequently, our PCA, NJ-tree, and Admixture population structure analyses of the 3 wool color Qira sheep populations showed that the 3 middle wool color populations exhibited the same genetic traits. Fst, xp-EHH, iHS, and π were detected for selection signals, and the 5% SNPs loci positively selected from the analyses were annotated based on SheepOar_v4.0. The region of exon 1 of the TYRP1 gene was further screened, amplified and sequenced through the DNA of the Qira sheep and associated with goodness-of-fit using the chi-square test. Results: The results showed that 71 SNPs associated with black wool traits, among which TYRP1, PARD3 and CDH2 genes were strongly associated with black wool production. Three mutations were detected in the exon 1 region of the TYRP1 gene that were significantly associated with coat color variation inQira sheep (2:81,183,168, 2:81,183,281 and 2:81,183,284). Conclusion: In this paper, Qira sheep could not differentiate the genetic structure of this population by wool color, and obtained 71 SNPs related to black wool. Detection of mutation sites on the TYRP1 gene affecting hair color change provides a basis for black sheep line selection as well as breed conservation. [ABSTRACT FROM AUTHOR]

AbstractFaba bean is susceptible to several foliar fungal diseases: ascochyta blight (Ascochyta fabae), alternaria leaf spot (Alternaria sp.), chocolate spot (Botrytis cinerea and Botrytis fabae), anthracnose (Colletotrichum lentis) and stemphylium blight (Stemphylium spp.). Under conducive conditions these diseases can cause significant economic losses. Visual diagnosis based on the appearance of lesions on faba beans is problematic, especially as they progress. The purpose of this study was to develop a multiplex polymerase chain reaction assay to detect the causal organisms of these diseases. Five pairs of primers, AFF7/AFR7 for A. fabae, BCF1/BCR1 for B. cinerea, BFF2/BFR2 for B. fabae, ClF2/ClR2 for C. lentis and Stem_F_S/Stem_R_S for Stemphylium spp. were developed. The previously developed primer pair aagpf1/aagpr1 was used to detect Alternaria sp. The primers were tested for specificity to their target pathogen and primer pairs AFF6/AFR6, aagpf1/aagpr1, BCF1/BCR1, BFF2/BFR2 and ClF2/ClR2 identified their target pathogens. The primer pair Stem_F_S/Stem_R_S identified S. beticola, S. botryosum, S. eturmiunum and S. vesicarium. Identification of pathogens with primers was evaluated using DNA from mycelia and from infected faba bean leaves generated through artificial inoculations under controlled conditions and collected from the field. A multiplex PCR assay with six primer pairs allowed for detection of the target pathogens to the species level for five pathogens, and to the genus level for species causing stemphylium blight. This assay enables quick diagnosis of leaf spots on faba bean, and minimizing time and effort needed to identify the primary cause of the infection through traditional isolation procedures. [ABSTRACT FROM AUTHOR]

Aspergillus fumigatus (Af) is a major mould pathogen found ubiquitously in the air. It commonly infects the airways of people with cystic fibrosis (CF) leading to Aspergillus bronchitis or allergic bronchopulmonary aspergillosis. Resident alveolar macrophages and recruited neutrophils are important first lines of defence for clearance of Af in the lung. However, their contribution to the inflammatory phenotype in CF during Af infection is not well understood. Here, utilising CFTR deficient mice we describe a hyperinflammatory phenotype in both acute and allergic murine models of pulmonary aspergillosis. We show that during aspergillosis, CFTR deficiency leads to increased alveolar macrophage death and persistent inflammation of the airways in CF, accompanied by impaired fungal control. Utilising CFTR deficient murine cells and primary human CF cells we show that at a cellular level there is increased activation of NFκB and NFAT in response to Af which, as in in vivo models, is associated with increased cell death and reduced fungal control. Taken together, these studies indicate that CFTR deficiency promotes increased activation of inflammatory pathways, the induction of macrophage cell death and reduced fungal control contributing to the hyper-inflammatory of pulmonary aspergillosis phenotypes in CF. Author summary: The airways of people with cystic fibrosis (pwCF) are commonly colonised with Aspergillus fumigatus (Af) resulting in a persistent hyperinflammatory state and the development of allergy. Understanding how first line defence innate cells, such as alveolar macrophages and neutrophils, contribute to this hyperinflammatory phenotype is important in developing novel treatments to preserve lung function in pwCF. In this study, we report that CFTR deficiency leads to increased alveolar macrophage death and persistent inflammation of the airways in pwCF, which is associated with impaired control of infection. We identify the increased activation of the transcription factors NFκB and NFAT as the mechanism of increased inflammatory cytokine production in CFTR deficient cells. This work represents major step in describing the molecular mechanisms of hyperinflammation in CF in response to fungal infection and lays the groundwork for further dissection of inflammatory pathways to target with immunotherapeutic approaches. [ABSTRACT FROM AUTHOR]

Introduction Febrile neutropenia is a dreadful complication associated with malignancies. Knowledge of locally prevalent pathogens and their resistance pattern is of paramount importance in guiding antimicrobial therapy. Objectives The aim of the study was to identify the common infectious agent, antibiotic susceptibility of culture positive patients, and outcome Materials and Methods We conducted a single-center prospective observational study. Forty-three children with febrile neutropenia episodes admitted in KKCTH, Chennai, were included in the study. The duration of the study was 1 year. Relevant patient and disease specific details were obtained, results were analyzed, and conclusions were drawn. Results There were 90 episodes of febrile neutropenia. Overall culture positivity was identified in 37 cases (41.11%). Bacteremia (23.3%) was the most common cause of microbiologically documented infection. Gram-positive organisms (60%) were more commonly documented. Among the gram-positive organisms, coagulase-negative Staphylococcus aureus was the predominant isolate followed by Streptococcus. Central line–associated bloodstream infections were documented in 13.33%. Chemo-port removal was done in four children. Three had invasive fungal disease. The majority of the gram-negative isolates were resistant strains. Morbidity was significantly more in gram-negative infections. Overall outcome was good though three children succumbed to sepsis. Conclusion A vigilant management of illness is essential. Chemo-port carries risk of severe infection. Protocol-based management of catheter-related bloodstream infection (CRBSI) can limit the number of chemo-port removal. Though gram-positive organisms are in the rise, gram-negative organisms are still responsible for significant morbidity. Early initiation of broad-spectrum empirical antibiotics with optimal gram-positive coverage is crucial. Children with suspected fungal infections should be aggressively evaluated and treated. An organized approach is the key in successful management. [ABSTRACT FROM AUTHOR]

The dynamic interplay between pathogens and host immune system determines the outcome of fungal infections. This study investigates the role of Ubp5 in modulating host defenses during Cryptococcus neoformans H99 infections. Ubp5 deletion significantly reduces both pulmonary invasion and extrapulmonary dissemination, resulting in prolonged survival and decreased fungal burdens in mice. Attenuated virulence is closely associated with enhanced host immune responses, rather than diminished pathogen fitness alone. Histopathological and leukocyte analyses revealed a shift towards protective adaptive immune responses in ubp5Δ-infected lungs, characterized by lymphocyte-dominated inflammatory infiltration and an increased Th1/Th17 cytokine response. Under host-associated conditions, ubp5Δ mutants exhibited morphological changes, including distorted shapes and cell wall heterogeneity, alongside defects in key virulence factors such as the polysaccharide capsule and melanin. These changes likely promote exposure of immunostimulatory cell wall components, enhancing host immunity. Additionally, Ubp5 deletion resulted in a significant reduction in intracellular ribosomal particles in C. neoformans, which likely impairs protein synthesis, contributing to reduced growth and pathogenic fitness in vivo. These findings underscore the pivotal role of Ubp5 in maintaining cryptococcal virulence and suggest that targeting Ubp5 could enhance host immunity against cryptococcosis by promoting protective immune responses and limiting fungal dissemination. [ABSTRACT FROM AUTHOR]

Fungal infections are a major contributor to mortality for people with HIV/AIDS. Recently, researchers, clinicians, industry experts, and policymakers convened for the triennial AIDS-Related Mycoses Meeting to address critical gaps in the management of AIDS-related mycoses. Delegates highlighted several scientifically driven milestones that have significantly reduced fungal-related deaths, and the need to address outstanding challenges in diagnosis, treatment, and research. [ABSTRACT FROM AUTHOR]

The prevalence of invasive fungal infections (IFIs) has risen in the past 3 decades, attributed to advancements in immune-modulatory therapies used in transplantation, rheumatology, and oncology. Organisms that cause IFI evade the host's natural defenses or at opportunities of immunologic weakness. Infections occur from inhalation of potentially pathogenic organisms, translocation of commensal organisms, or reactivation of latent infection. Organisms that cause IFI in immunocompromised populations include Candida species, Cryptococcus species, environmental molds, and endemic fungi. Diagnosis of these infections is challenging due to slow organism growth and fastidious culture requirements. Moreover, fungal biomarkers tend to be nonspecific and can be negatively impacted by prophylactic antifungals. Antibody-based tests are not sensitive in immunocompromised hosts making antigen-based testing necessary. Prevention of IFI is guided by pathogen avoidance, removal or minimization of immune-suppressing factors, and pharmacologic prophylaxis in select hosts. Understanding the complex interplay between the immune system and opportunistic fungal pathogens plays a key role in early diagnosis and prevention. [ABSTRACT FROM AUTHOR]

Background: Basidiobolomycosis is a rare fungal infection caused by Basidiobolus ranarum. Case Presentation: A 53-year-old man from Saudi Arabia with a known history of diverticulosis presented with severe abdominal pain and diarrhea. A CT scan revealed circumferential wall thickening of the descending and sigmoid colon with surrounding fat stranding, suggesting a diagnosis of complicated diverticulitis. Additional thick fluid was observed around the affected area. Surgical excision was pursued. A gross examination of two received large bowel segments disclosed marked ulcerated mucosa and wall thickening with exudate-covered serosal surfaces and adhesions. Microscopic examination unveiled significant infiltration by eosinophils, polymorphonuclear leukocytes, and granulomatous inflammation. Thin-walled, broad fungal hyphae of Basidiobolus, surrounded by eosinophilic material, were identified. Granulomas displayed abundant multinucleated giant cells and palisading histiocytes around central necrosis or abscess formation. Thin-walled, broad fungal hyphae of Basidiobolus, with sparse septations, are surrounded by a radiating, intensely eosinophilic cuff (Splendore-Hoeppli phenomenon). These hyphae, visible with hematoxylin and eosin staining, were further highlighted with periodic acid-Schiff and Gomori methenamine silver staining. Discussion: Basidiobolomycosis may mimic neoplastic lesions. Histologically, the characteristic features include broad, thin-walled septate hyphae surrounded by eosinophilic material, a finding that is accentuated by the Splendore-Hoeppli phenomenon. Microscopic examination, along with special stains such as periodic acid-Schiff (PAS) and Gomori methenamine silver, is essential for accurate diagnosis. Conclusion: Prompt recognition and appropriate antifungal therapy are vital for favorable patient outcomes. This report highlights the distinctive features of Basidiobolomycosis to raise awareness and understanding of this infrequent yet clinically significant fungal infection. [ABSTRACT FROM AUTHOR]

Introduction: In 2022, the World Health Organization published a report encouraging researchers to focus on Candida spp. to strengthen the global response to fungal oral infections and antifungal resistance. In the context of innovative research, it seems pertinent to investigate the antifungal potential of natural extracts of plants and the methodology involved in the recent reports. The aim of this systematic review is to identify the current state of in vitro research on the evaluation of the ability of plant extracts to inhibit Candida spp. Material and methods: A bibliographic search has been developed to on a 10-year period to identify which plant extracts have an antifungal effect on the Candida spp. found in the oral cavity. Results: A total of 20 papers were reviewed and fulfilled all the selection criteria and were included in the full data analysis. Discussion: Plants have been tested in a wide range of states - whole extracts, extraction of particular components such as flavonoids or polyphenols, or even using the plant to synthesize nanoparticles. Of forty-five plants tested, five of them did not show any effect against Candida spp., which weren't part of the same family. There is a wide range of plant that exhibit antifungal proprieties. Conclusion: Many plants have been tested in a wide range of states - whole extracts, extraction of components such as flavonoids or polyphenols, or even using the plant to synthetize nanoparticles. The combination of plants, the addition of plants to a traditional antifungal and the interference with adhesion provided by some plants seem to be promising strategies. Nonetheless, on contrary to drugs, there is a critical lack of standardization on methodologies and protocols, which makes it difficult to compare data and, consequently, to conclude, beyond doubts, about the most promising plants to fight Candida spp. oral infections. [ABSTRACT FROM AUTHOR]

Infections after orthotopic heart transplantation (OHT) cause significant morbidity and mortality. Concurrent with increased pre-OHT temporary mechanical circulatory support (MCS), there have been recent concerns of a perceived increase in infections post-OHT. We examined the association between pre-OHT temporary versus durable MCS and post-OHT infection. We performed a single-center retrospective review of patients who received OHT at Tufts Medical Center between January 2014 and April 2022. Our composite outcome was the occurrence of bacteremia, invasive fungal infections, opportunistic infections, or skin/soft tissue infections of device sites within 1-year post-OHT. We used Cox proportional hazards models to assess the relationship between the type of pre-OHT MCS and time to the first infection, treating death from other causes as a competing risk. We addressed confounding with 2 statistical methods: propensity score (PS) with inverse probability weighting (IPW) and an instrumental variable (IV) analysis. Of the 320 OHT recipients, 268 required MCS before OHT; 192 were managed with durable MCS and 76 with temporary MCS. Patients receiving pre-OHT temporary MCS had no difference in time to first infection (unadjusted hazard ratio [HR] 0.77, 95% CI 0.41-1.44) compared to durable MCS. Results were similar in the model employing PS with IPW (HR 0.61, 95% CI 0.29-1.27) and the IV analysis (HR 0.28, 95% CI 0.26-2.36). Pre-OHT temporary MCS was not associated with the composite outcome of bacteremia, invasive fungal infections, opportunistic infections, or skin/device site infections post-OHT compared to durable MCS in this single-center cohort. [ABSTRACT FROM AUTHOR]

Beauveria bassiana AAD16, isolated from Allomyrina dichotoma, shows promise as a mycoinsecticide against various coleopterans. However, assessing non-target impacts on beneficial beetles like ladybirds is crucial before commercialization. Here we assessed the compatibility between ladybird beetles and B. bassiana AAD16. The virulence of the AAD16 strain was compared with that of an available commercial strain, B. bassiana GHA, for two developmental stages (adults and 3rd instar larvae) of two coccinellids, Harmonia axyridis Pallas and Chilocorus spp. Say using the topical (1μl) application method. The ST50 for the two life stages of the two ladybird beetles were not different between the two tested fungal strains. Mycosis rates recorded from the dead bodies were also not significant except in the 3rd instar which showed 36 and 63% from AAD16 and GHA strains in H. axyridis, while those of Chilocorus spp. were 40 and 63%, respectively. In adult stage, the mycosis rates of H. axyridis (males and females tested separately) were (20–23) % and (26–30) % from the AAD16 and GHA strains, while those of Chilocorus spp. (unsexed) were 23 and 30%, respectively. AAD16 caused similar rates of mortality in the adult stages of both species. Therefore, we conclude that B. bassiana AAD16 would not increase risk to these beneficial insects compared to a similar pathogen commercialized. [ABSTRACT FROM AUTHOR]

Candida albicans is a commensal fungus that naturally inhabits the vagina. However, overgrowth of C. albicans can result in vulvovaginal candidiasis (VVC), one of the most prevalent fungal infections affecting women. The rapid emergence of azole resistance in C. albicans, in addition to the limited available antifungal agents, complicates the treatment and emphasizes the urgent need for novel therapeutic options. Efflux-mediated azole resistance is a common resistance mechanism in fluconazole (FLZ)-resistant C. albicans. Combination therapy using natural compounds is a potential approach that can restore fluconazole's antifungal activity in azole-resistant isolates via efflux pump inhibition. This study aimed to evaluate the ability of celastrol, a natural triterpene, to retrieve FLZ antifungal activity against azole-resistant C. albicans in vitro and in vivo. Celastrol did not exhibit antifungal activity against the tested clinical isolates; however, the sub-MIC of celastrol inhibited rhodamine 6G (R6G) efflux and increased R6G accumulation inside celastrol-treated C. albicans cells. Synergy was spotted between celastrol and FLZ via a checkerboard assay. Quantification of m-RNA levels of efflux-mediated azole resistance genes within azole-resistant C. albicans demonstrated CDR1 overexpression. Upon celastrol treatment, a significant decline in ABC transporters transcript levels were detected. Moreover, molecular docking demonstrated that celastrol is a potential ABC efflux transporters blocker that successfully fits into target binding pockets. A negligible hemolytic effect of celastrol against human erythrocytes was observed. In the in vivo model of VVC, the combination of FLZ and celastrol in vaginal gel revealed a drastic reduction in the fungal burden with apparently normal vaginal tissue. Celastrol promising in vitro and in vivo findings strengthen its future use for the treatment of azole-resistant C. albicans. [ABSTRACT FROM AUTHOR]

Malachite green (MG) is used as a dye for materials such as wood, cotton, and nylon, and is used in aquaculture to prevent fungal and protozoan diseases. However, it is highly toxic, with carcinogenic, mutagenic, and teratogenic properties, resulting in bans worldwide. Despite this, MG is still frequently used in many countries due to its efficacy and economy. MG is persistent in the environment and so requires degradative intervention. In this work we isolated Bacillus pacificus ROC1 strain from a salt flat in Pakistan that had the ability to aerobically detoxify MG, as determined by bacterio- and phyto-toxicity assays. We demonstrate immobilized B. pacificus ROC1 can effectively detoxify MG, which highlights a potential method for its biodegradation. Genomic sequencing identified three candidate azo-reductases within B. pacificus ROC1 that could be responsible for the MG-degrading activity. These were cloned, expressed and purified from Escherichia coli, with one (AzrC), catalyzing the reduction of MG to leuco-MG in vitro. AzrC was crystallised and MG was captured within the active site in a Michaelis complex, providing structural insight into the reduction mechanism. Altogether, this work identifies a bacterium capable of aerobically degrading a major industrial pollutant and characterizes the molecular basis for this activity. [ABSTRACT FROM AUTHOR]

Background: Fungal invasive infections caused by Candida species pose a substantial public health risk with limited therapeutic options. Antifungal susceptibility testing (AFST) is necessary to optimize the therapy. The study aimed to compare different AFST methods of Candida spp. and detect FKS gene mutations among caspofungin-intermediate and resistant isolates. Methods: A total of 60 non-replicative invasive Candida isolates recovered from various clinical samples were included. In-vitro AFST was carried out using the ATB FUNGUS 3, Vitek-2 AST-YS08, and E-test. Hotspot (HS) regions of FKS genes were sequenced for caspofungin-intermediate and resistant isolates. Results: Candida albicans (58.3%) was the most predominant spp., followed by C. glabrata (28.3%). Based on the clinical breakpoints (CBPs), fluconazole resistance was found in C. albicans (45.7%), C. tropicalis (25%), and the C. parapsilosis isolate, while 35.3% of C. glabrata were susceptible dose-dependent (SDD). None of C. albicans, C. tropicalis, or C. parapsilosis isolates were resistant to voriconazole. Using the epidemiological cut-off values (ECVs) for amphotericin B, 6.7% of isolates were non-wild type (non-WT), including C. guilliermondii (50%), C. tropicalis (25%), and C. glabrata (11.8%), while all C. albicans, C. parapsilosis, and C. kefyr isolates were classified as wild-type (WT). ATB FUNGUS 3 and Vitek-2 had the highest categorical agreement (CA) (83.1%) for amphotericin B, while a lower concordance was detected with voriconazole (23.2%) and fluconazole (52.2%). For caspofungin, Vitek-2 and E-test had a CA of 89.8%. Eleven isolates (10 C. glabrata and one C. parapsilosis) exhibited resistance or intermediate susceptibility to caspofungin (MICs: 0.25‒>32 µg/ml). Molecular characterization of the FKS gene demonstrated that FKS1 mutations V47I, V52K, V56T, D57S, L62F, I71Y, I71Q in the HS1 region, and G7S, P11H mutations in the HS2 region were associated with increased caspofungin MIC values (16 µg/ml). Mutations at the HS1 of the FKS2 gene; K33V, W35K, and W35V; were associated with the highest caspofungin MICs of > 32 µg/ml. Conclusions: ATB FUNGUS 3 demonstrated acceptable performance for AFST, however, azole activity against Candida spp. should be interpreted carefully. Novel mutations within HS regions of FKS genes elucidated different levels of caspofungin resistance in C. glabrata and C. parapsilosis isolates. [ABSTRACT FROM AUTHOR]

The article discusses the increasing prevalence of Valley fever, a fungal infection caused by Coccidioides spores, in the Southwest, particularly in Arizona and California. The disease can range from mild flu-like symptoms to severe, lifelong lung infections or disseminated disease affecting bones, joints, or skin. Factors contributing to the rise in cases include climate change, population growth, and changes in reporting and diagnostic methods. Researchers are studying the spread of the fungus, potential transmission routes, and developing vaccines to prevent infections. The personal stories of individuals affected by Valley fever highlight the severity and long-term consequences of the disease. [Extracted from the article]

Background Mucormycosis is an aggressive invasive fungal infection caused by molds in the order Mucorales. Early diagnosis is key to improving patient prognosis, yet it relies on insensitive culture or nonspecific histopathology. A pan-Mucorales–specific monoclonal antibody (mAb), TG11, was recently developed. Here, we investigate the spatiotemporal localization of the antigen and specificity of the mAb for immunohistochemistry. Methods We used immunofluorescence microscopy to assess antigen localization in 11 Mucorales species of clinical importance and live imaging of Rhizopus arrhizus germination. Immunogold transmission electron microscopy revealed the subcellular location of mAb TG11 binding. Finally, we performed immunohistochemistry of R arrhizus in an ex vivo murine lung infection model alongside lung infection by Aspergillus fumigatus. Results Immunofluorescence revealed TG11 antigen production at the emerging hyphal tip and along the length of growing hyphae in all Mucorales except Saksenaea. Time-lapse imaging revealed early antigen exposure during spore germination and along the growing hypha. Immunogold transmission electron microscopy confirmed mAb TG11 binding to the hyphal cell wall only. The TG11 mAb stained Mucorales but not Aspergillus hyphae in infected murine lung tissue. Conclusions TG11 detects early hyphal growth and has valuable potential for diagnosing mucormycosis by enhancing discriminatory detection of Mucorales in tissue. [ABSTRACT FROM AUTHOR]

The scientific interest in the chemical modification of chitosan to increase its solubility and application has led to its conjugation with Schiff bases, which are interesting scaffolds endowed with diverse biological properties. The resultant chitosan-based Schiff bases (CSBs) are widely studied in scientific literature due to the myriad of activities exerted, both catalytic and biological, including anticancer, anti-inflammatory, antioxidant, and especially antimicrobial ones. Antimicrobial resistance (AMR) is one of the major public health challenges of the twenty-first century because it represents a threat to the prevention and treatment of a growing number of bacterial, parasitic, viral, and fungal infections that are no longer treatable with the available drugs. Thus, in this review, we present a brief outline of the biological activities of CSBs as well as their complexes with metals, with a particular focus on the recent literature regarding the antimicrobial effect of these captivating derivatives. [ABSTRACT FROM AUTHOR]

Background/Objective: Tinea capitis is a common scalp fungal infection with significant implications for public health, particularly in regions where proper hygiene and access to healthcare are limited. Emerging evidence suggests that this disease, particularly in young male individuals, may be related to certain unsanitary practices in barbershop settings, such as the use of contaminated shaving equipment. To increase awareness of the risk of scalp dermatophyte infections by disclosing different cases of tinea capitis that had arisen shortly after hairdressing procedures and providing a comprehensive review of the existing literature. Patients and Methods: 10 cases of young, adult male patients developed tinea capitis after haircuts carried out at different local barbershops in Sardinia. A collection of data regarding age, sex, location of the disease, clinical manifestations as well as direct microscopy and cultural investigations were performed. Results: Clinical manifestations varied among patients, exhibiting both non-inflammatory and inflammatory features, cultural investigations were positive for Trichophyton tonsurans. Patients were treated with griseofulvin or terbinafine in combination with topical antimycotics. Two cases out of the ten patients developed scarring alopecia. Conclusions: Outbreaks of T. tonsurans-induced tinea capitis, linked to hairdressing, have been recorded in many different countries. Timely diagnosis and therapy are crucial, since any delay can result in disease dissemination and potential complications such as scarring alopecia, particularly in the inflammatory forms. [ABSTRACT FROM AUTHOR]

Background: Macrophomina phaseolina is an important phytopathogenic fungus affecting over 500 plant species worldwide. However, this fungus rarely causes disease in humans. Methods: We reported the first case of endophthalmitis due to M. phaseolina, describing microbiological diagnostic approaches. Also, we performed a systematic review of human infections by this plant pathogen in literature. We searched PubMed, Scopus, and Web of Science databases from inception to 31 December 2024. Results: Our case involved a male patient who presented with photophobia and pain in his right eye. His recent medical history revealed a superficial corneal injury caused by a metal burr three months prior, managed unsuccessfully by topical treatment and subsequent conjunctival flap surgery two months later. Ophthalmological and microbiological investigations, including microscopic examination, cultures, and DNA sequencing of ocular specimens, revealed M. phaseolina endophthalmitis. Despite intravenous and intravitreal antifungal therapy, the patient's condition continued to worsen, eventually leading to enucleation. Regarding the literature review, we identified 12 additional cases of M. phaseolina human infections previously reported in literature. Overall, M. phaseolina was primarily associated with ocular infections (76.9% of cases), followed by skin infections and combined skin–joint infections. The majority of patients with M. phaseolina infection (63.6%) had no known immunosuppressive factors. Clinical outcomes were unfavorable in 46.15% of cases. Conclusions: M. phaseolina is an emerging cause of human infections, even in immunocompetent hosts, with a predilection for ocular infections. Further research is warranted to elucidate the pathogenesis of fungal infections caused by plant pathogens in humans. [ABSTRACT FROM AUTHOR]

In immunocompromised patients, pneumonia presents a diagnostic challenge due to diverse etiologies, nonspecific symptoms, overlapping radiological presentation, frequent co-infections, and the potential for rapid progression to severe disease. Thus, timely and accurate diagnosis of all pathogens is crucial. This narrative review explores the latest advancements in microbiological diagnostic techniques for pneumonia in immunocompromised patients. It covers major available microbiological tools for diagnosing both community-acquired and hospital-acquired pneumonia, encompassing a wide spectrum of pathogens including bacterial, viral, fungal, and parasitic. While traditional culture methods remain pivotal in identifying many pneumonia-causing etiologies, their limitations in sensitivity and time to results have led to the rise of non-invasive antigen tests and molecular diagnostics. These are increasingly employed alongside cultures and microscopy for more efficient diagnosis, mainly in viral and fungal infections. Lastly, we report the future of pneumonia diagnostics, exploring the potential of metagenomics and CRISPR/Cas13a for more precise and rapid pathogen detection in immunocompromised populations. [ABSTRACT FROM AUTHOR]

Simple Summary: Amphibians around the world are at risk due to a deadly fungal infection caused by Batrachochytrium dendrobatidis (Bd). This study reports a relevant Bd detection in amphibians within two protected areas in northwestern Italy, specifically near Turin. The investigation was prompted by an unusual number of common toad deaths, which led to further analysis of other amphibians sampled in the area. Testing revealed that Bd was present in 38.6% of the sampled amphibians, with higher positivity rates in La Mandria Park compared to the Vauda protected area. However, while Bd was identified, the exact cause of the observed mortality remains uncertain and may involve other pathogens or multifactorial causes. This represents the first reported case of Bd detection in Piedmont in 18 years, underscoring the ongoing threat this pathogen poses to local wildlife. The results highlight the need for comprehensive monitoring and conservation efforts to protect vulnerable amphibian species from Bd and other potential threats. Chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), is a significant threat to global amphibian populations, leading to widespread declines and extinctions. In the spring of 2023, Bd presence was detected in different amphibian species within two protected areas near Turin, Piedmont, Italy, following an unusual mortality event among the common toad (Bufo bufo). Histological and molecular analyses confirmed Bd infection in a deceased Pelophylax sp. specimen, prompting further investigation. Sampling of 166 individuals across seven amphibian taxa revealed an overall Bd occurrence of 38.6%, with Pelophylax sp. showing the highest detection rate (50.5% of 93 individuals). A marked difference in the positivity rate was observed between the two locations, with La Mandria (67.2% of 58) exhibiting significantly higher rates than Vauda (22.9% of 35). While Bd was identified in the sampled amphibians, the exact cause of the observed mortality remains unclear and may involve other pathogens or multifactorial causes, including but not limited to Bd. These findings represent the first documented case of Bd presence in Piedmont after an 18-year gap, highlighting the potential influence of local environmental factors on infection dynamics. The study emphasises the need for expanded, standardised field sampling and further investigation into the various factors affecting amphibian health to guide conservation efforts for vulnerable amphibian species. [ABSTRACT FROM AUTHOR]

Background/Objectives: Candida auris is an emerging multidrug-resistant pathogen with the potential to cause invasive fungal infections and healthcare-associated outbreaks. Currently, there is no systematic review explicitly focusing on the up-to-date molecular diagnostics of this pathogen to cover the entire process, including sample pre-extraction procedures, nucleic acid extraction, and DNA-based detection. Sample pre-treatment and extraction are the prerequisites before molecular testing and have implications on the downstream detection but have not been reviewed elsewhere. This review aims to summarize a comprehensive update in the past 5 years. Methods: A systematic review was conducted to search for articles published in the period between 1 January 2020 and 20 November 2024 from various databases, including PubMed, Google Scholar, and Web of Science. The findings were produced through narrative synthesis, with quantitative analysis conducted where applicable. Results: Starting from 1115 records, 28 studies that met the inclusion criteria were included in the analysis. This review summarized the key updates on three categories, including (i) sample pre-extraction procedures and nucleic acid extraction, including magnetic, bead-beating, mechanical, chemical, thermal, and column-based protocols; (ii) commercial molecular assays; and (iii) laboratory-developed tests (LDTs). For real-time PCR, commercial molecular assays and LDTs showed sensitivity (ranging from 94.9% to 100% and 44% to 100%, respectively) and specificity (ranging from 98.2% to 100% and 92% to 100%, respectively). Conclusions: Here, we describe a useful summary to enlighten readers from clinical microbiology laboratories on the nucleic acid extraction protocols and performance of various molecular diagnostic assays used for the detection of C. auris. [ABSTRACT FROM AUTHOR]

Hematologic malignancies, diabetes, and the development and widespread use of novel anticancer and immunosuppressive agents have introduced a new dimension of immunosuppression, raising concerns about emerging opportunistic infections. Here, we report a case of mucormycosis in a patient with therapy-related acute myeloid leukemia, encountered in our department. The patient presented with a necrotic lesion around the right eyelid. In this case, the condition and skin lesions rapidly progressed, and the patient passed away within a few days of the appearance of necrotic plaques. The causative organism was identified as Rhizopus microsporus. Mucormycosis is a severe invasive fungal infection that can rapidly worsen the prognosis of immunocompromised patients. Cutaneous mucormycosis is classified into primary and secondary forms. Based on the findings and the underlying disease, secondary cutaneous mucormycosis was suspected. Familiarity with the characteristic clinical features of mucormycosis may be the key factor in initiating timely treatment. [ABSTRACT FROM AUTHOR]

Fungal trunk diseases are of major concern for tree fruit, nut, and grape growers throughout the world. These diseases include Eutypa dieback of grape, caused by Eutypa lata, band canker of almond, caused by Neofusicoccum mediterraneum and Neofusicoccum parvum, and twig and branch dieback of walnut, caused by N. mediterraneum, Botryosphaeria dieback of grape, caused by Diplodia mutila, Diplodia seriata, N. mediterraneum, and N. parvum, and esca of grape, caused by Phaeomoniella chlamydospora and Phaeoacremonium minimum. Given the common occurrence of mixed infections, and the similar wood symptoms at the macroscopic level, species-specific detection tools are needed. Fatty acid methyl ester (FAME) profiling can be an effective and inexpensive diagnostic tool. FAME analyses were conducted on pure cultures of multiple isolates per species to characterize profiles and assess whether this technique could result in consistent identification. FAME profiles were dominated by oleic acid (18:1 ω9c) and palmitic acid (16:0), with less abundant FAMEs in different ratios for each species and isolates within species. Canonical discriminant analyses revealed which minor FAMEs were most variable, with a total of 20 different FAMEs that can explain 69.01% of profile variance in the first two canonicals. Using these analyses, samples were self-tested and correctly sorted 97.18% of the time. Within species, canonical discriminant analyses were able to separate isolates further, often by original geographic location or by host plant species. These results further suggest that potential novel species, subspecies, or races may be present among the isolates analyzed, demonstrating the capacity of FAME profiling to have a role in discovering cryptic species and accurately identifying fungal pathogens in conjunction with other molecular techniques and genomic analyses. [ABSTRACT FROM AUTHOR]

Background: Chronic pulmonary abscess usually results from bacterial or mycobacterium infection, but rarely from aspergillosis. Chronic pulmonary aspergillosis is usually found in a person with structural lung disease or immunocompromise. Here, we report a case of chronic lung abscess of aspergillosis without immunocompromise, structural lung diseases or even clinical symptoms. Case presentation: A 43-year-old female was found a mass shadow with central liquid anechoic area in the apical posterior segment of the left upper lung lobe by chest computerized tomography for 1 month, but had no any systematic or respiratory complaints. The percutaneous abscess puncture was performed and 30 milliliters of yellow purulent fluid were aspirated from the liquid anechoic area. Then Aspergillus terreus was detected by both fluid culture and metagenomics next-generation sequencing. Interestingly, this patient had no history of tuberculosis or chronic pulmonary diseases. Other immunocompromised conditions were also denied through history inquest and laboratory tests. Ultimately, the catheterization and drainage of the lung abscess and 6 months of antifungal therapy with standard dose of voriconazole brought the woman a favorable outcome. Conclusion: Aspergillus lung abscess can occasionally occur in a person without pre-existent lung cavity and immune suppression, which is prone to misdiagnosis because of the rarity and the symptom-free. [ABSTRACT FROM AUTHOR]

Background: Postharvest lemons are affected by several fungal infections, and as alternatives to chemical fungicides for combating these infections, different microbial biocontrol agents have been studied, with the Clavispora lusitaniae 146 strain standing out. Although strain 146 has proven to be an effective agent, the influence of a microbial biological control agent on the postharvest lemon microbiome has not been studied until now. Thus, this study aimed to evaluate how the epiphytic microbiome of postharvest lemons is affected by the application of the biocontrol yeast C. lusitaniae 146. Results: In terms of bacterial composition, the most abundant genera were Sphingomonas, Pelomonas, and Bacillus and no significant differences in the composition were detected between the treated and control samples. Among fungi, Clavispora was predominant not only in the treated samples but also in the control, and statistics indicated differences, suggesting its significant role in modulating the epiphytic community composition of lemon. Understanding fruit microbiomes is vital for effective disease control, and this study provides insights into the microbial composition of the surface of lemon and the role of C. lusitaniae 146. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: The bacterial organism Capnocytophaga canimorsus is an oral commensal of cats and dogs and can cause lifethreatening infections like mycotic aneurysm, meningitis, and sepsis. Mycotic aneurysms occur when microbial infections cause arterial wall degeneration. Difficulty in diagnosing Capnocytophaga canimorsus infection can occur due to the bacteria's fastidious nature and laboratory testing limitations, contributing to the infection's high morbidity and mortality. This report describes the case of a patient with an iliac artery mycotic aneurysm 2 months after a dog bite. Identification of Capnocytophaga canimorsus was achieved through polymerase chain reaction. Case Report: The 67-year-old female patient presented initially with nonspecific abdominal pain. Imaging revealed a right iliac artery abnormality suspicious for mycotic aneurysm. Capnocytophaga canimorsus was identified through broad-range bacterial polymerase chain reaction after standard culture failed to determine the infectious etiology. A history of dog bite was discovered after diagnosis. When standard culture cannot provide a diagnosis, 16s rRNA polymerase chain reaction is the preferred molecular-based test at our institution. Conclusions: Through presentation of a case of Capnocytophaga canimorsus mycotic aneurysm in an immunocompetent woman, this report illustrates the importance of familiarity with Capnocytophaga canimorsus and molecular laboratory methods in achieving favorable outcomes when faced with Capnocytophaga canimorsus infection. In these difficult cases, 16s rRNA polymerase chain reaction and similar molecular technologies are becoming essential. This case also highlights thorough history-taking as essential for guiding correct diagnosis and reinforces that infection with Capnocytophaga canimorsus should be investigated when there is a history of dog bite. [ABSTRACT FROM AUTHOR]

Invasive fungal infections are a leading cause of death worldwide. Translating molecular insights into clinical benefits is challenging because fungal pathogens and their hosts share similar eukaryotic physiology. Consequently, current antifungal treatments have limited efficacy, may be poorly fungicidal in the host, can exhibit toxicity, and are increasingly compromised by emerging resistance. We have established that the phosphatase calcineurin (CaN) is required for invasive fungal disease and an attractive target for antifungal drug development. CaN is a druggable target, and there is vast clinical experience with the CaN inhibitors FK506 and cyclosporin A (CsA). However, while FK506 and its natural analog FK520 exhibit antifungal activity, they are also immunosuppressive in the host and thus not fungal-selective. We leverage our pathogenic fungal CaN-FK506-FKBP12 complex X-ray structures and biophysical data to support structure-based ligand design as well as structure-activity relationship analyses of broad-spectrum FK506/FK520 derivatives with potent antifungal activity and reduced immunosuppressive activity. Here, we apply molecular docking studies to develop antifungal C22-or C32-modified FK520 derivatives with improved therapeutic index scores. Among them, the C32-modified FK520 derivative JH-FK-44 (7) demonstrates a significantly improved therapeutic index compared to JH-FK-08, our lead compound to date. NMR binding studies with C32-derivatives are consistent with our hypothesis that C32 modifications disrupt the hydrogen bonding network in the human complex while introducing favorable electrostatic and cation-π interactions with the fungal FKBP12 R86 residue. These findings further reinforce calcineurin inhibition as a promising strategy for antifungal therapy. [ABSTRACT FROM AUTHOR]

Background: Bone infections such as chronic fungal erosive osteomyelitis are uncommon forms of bone infection. The endemic dimorphic fungus Coccidioides impact generally immunocompromised patients. These infections frequently have no symptoms and the clinical signs remain undetected, allowing the infection to worsen over weeks or months. Mycotic arthritis is one of the rarest clinical symptoms; it is hard to distinguish from other types of arthritis, which slows down the diagnosis procedure. Case presentation In order to demonstrate the beginning and progression of radiological abnormalities in a case of aggressive fungal osteomyelitis, we provide the case of a 31-year-old male patient here. The man showed signs of extensive bone erosion and inflammatory involvement in his right knee and right hallux phalanx, although he had no prior history of immunodeficiency. The infection resulting from Coccidioides Immitis in his right knee and in his hallux was the reason for the injuries. Conclusions: While an acute, benign, and self-eradicating lung infection is the predominant presentation for most cases of coccidioidomycosis, a small percentage of patients experience a devastating extrapulmonary condition, which can include arthritis. The pathogenic mechanism of bone involvement is unknown, and it often remains untreated. Here, we discuss radiographic evidence of particular bone inflammation during the early phase and later phases of the disease, since management of this chronic condition remains a challenge. We propose that imaging may mimic osseous neoplasia in persistent fungal diseases, such as coccidioidomycosis. [ABSTRACT FROM AUTHOR]

Background: Mucormycosis (MCR) is an uncommon but frequently deadly fungal infection that typically affects individuals with weakened immune systems. Pulmonary MCR, in particular, is most frequently observed in patients who have undergone stem cell or solid organ transplants. The incidence of MCR in solid organ transplant recipients is reported to be 0.07% within the first year. In almost 40% of these transplant patients, including the case we examined, the infection is diagnosed within the first 6 months after the transplant. Case Presentation: We report a rare case of a 67-year-old man who developed pulmonary MCR within 6 months after undergoing a heart transplant. A bronchoscopy was conducted, and Reverse transcription polymerase chain reaction along with cultures of the broncho-alveolar samples tested positive for Mucorales. After consulting with experts from thoracic and vascular surgery, cardiology, pulmonology, and microbiology, and adhering to the expert guidelines, a semi-urgent source control procedure was recommended. This involved performing a thoracoscopic exploration of the right pleura, which was subsequently converted to a lateral thoracotomy, culminating in the resection of the right lower lobe. Conclusion: Invasive MCR is a rare but serious fungal infection with a high risk of illness and death, particularly in people with underlying health issues or weakened immune systems. The clinical and imaging manifestations can vary among patients based on their immune status and how they contracted the infection. Despite these variations, it is vital to maintain a high level of suspicion for MCR, as early diagnosis and the rapid initiation of surgical and antifungal treatments are critical for improving survival chances. [ABSTRACT FROM AUTHOR]

Isolated maxillary fungal pathologies involve a variety of clinical entities. These include invasive and non-invasive variants, where each has a unique pathogenesis, clinical manifestation, and approach for management. The aim of this case series is to investigate the several ways that fungal infections of the maxillary sinus might present, with the approach to diagnose and manage these conditions. Several discrete maxillary fungal diseases were studied, including fungal ball, acute fulminant invasive fungal sinusitis, allergic fungal sinusitis, and chronic invasive fungal sinusitis at a hospital. For every condition, several treatment options, clinical manifestations, and diagnostic strategies were investigated, which are greatly influenced by the degree of invasiveness as well as the patient's immunological status. Optimizing patient outcomes, especially in more aggressive types of the disease, requires an early and proper diagnosis. Understanding the various symptoms of these fungal infections is critical for a timely management. [ABSTRACT FROM AUTHOR]

Laparoscopic cholecystectomy is the preferred method for treating acute cholecystitis. Although the incidence of postoperative infections in laparoscopic cholecystectomy is low, serious postoperative surgical site infections are still reported. Hepatic abscesses, particularly fungal, can occur post-cholecystectomy leading to significant mortality and morbidity. We report a case of a 58-year-old female who underwent laparoscopic cholecystectomy and subsequently developed fever, jaundice, and right upper quadrant pain. Laboratory results showed deranged liver function tests with raised inflammatory markers. Radiographic investigations, including CT and MRI, revealed an irregular hilar lesion with periportal changes suggestive of an abscess with portal vein thrombosis. Histopathological examination of the biopsy obtained from the hilar lesion showed a fungal hepatic infection, and particularly conidiobolomycosis. To our best knowledge, this is the first case that reports this fungal infection as a complication of laparoscopic cholecystectomy. The patient was managed with a combination of intravenous antibiotics and antifungals, which yielded mild improvement. Unfortunately, the patient decided to leave the hospital against medical advice, limiting the information on the disease course. [ABSTRACT FROM AUTHOR]

Berberine (BBR), an isoquinoline alkaloid found in medicinal plants such as Coptidis rhizoma, Berberis sp., and Hydrastis canadensis, is a distinctive compound known for its dual ability to exhibit broad-spectrum antifungal activity while offering beneficial effects to the host. These attributes make it a highly valuable candidate for antifungal therapy and as an antibiotic adjuvant. This review provides a comprehensive evaluation of BBR's antifungal properties, focusing on its in vitro and in vivo activity, underlying mechanisms, and its influence on fungal pathogenicity, including virulence, biofilm formation, and resistance. Additionally, the antifungal potential of BBR extracts, derivatives, and nanoformulations is examined in detail. BBR demonstrates fungicidal effects through multiple mechanisms. It targets critical fungal components such as mitochondria, cell membranes, and cell walls, while also inhibiting enzymatic activity and transcription processes. Furthermore, it suppresses the expression of virulence factors, effectively diminishing fungal pathogenicity. Beyond its direct antifungal activity, BBR exerts beneficial effects on the host by modulating gut microbiota, thereby bolstering host defenses against fungal infections and reducing potential adverse effects. BBR's interaction with conventional antifungal drugs presents a unique complexity, particularly in the context of resistance mechanisms. When used in combination therapies, conventional antifungal drugs enhance the intracellular accumulation of BBR, thereby amplifying its antifungal potency as the primary active agent. These synergistic effects position BBR as a promising candidate for combination strategies, especially in addressing drug-resistant fungal infections and persistent biofilms. As antifungal resistance and biofilm-associated infections continue to rise, the multifaceted properties of BBR and its advanced formulations highlight their significant therapeutic potential. However, the scarcity of robust in vivo and clinical studies limits a full understanding of its efficacy and safety profile. To bridge this gap, future investigations should prioritize well-designed in vivo and clinical trials to thoroughly evaluate the therapeutic effectiveness and safety of BBR in diverse clinical settings. This approach could pave the way for its broader application in combating fungal infections. [ABSTRACT FROM AUTHOR]

The article presents a proposed respiratory fungal culture protocol for bottlenose dolphins, addressing the growing concern of fungal infections in cetaceans and their impact on conservation efforts. It identifies various fungal species with diagnostic and clinical significance, detailing a comprehensive protocol for sampling, inoculation, identification, and susceptibility testing. Emphasizing the need for a robust fungal surveillance protocol, the authors discuss research articles covering diverse aspects of fungal infections in marine mammals, advocating for a One Health approach to combat emerging fungal diseases and antifungal resistance. The document also references the World Health Organization's fungal priority pathogens list and explores the phylogeny and ecology of the saprobe Cladosporium sphaerospermum. [Extracted from the article]

Background: Mucorales and Aspergillus have invasive fungal infections with high mortality, mainly in immunocompromised and diabetic patients. The diagnosis is microbiological and pathological, with a strong clinical suspicion. The treatment is medical and surgical debridement. Invasive fungal coinfection by these two is reported as a case report. Here, we highlight the importance of considering the coinfection of Aspergillus and Mucor in the maxillary bone and paranasal sinuses in patients with systemic lupus erythematosus (SLE). Cases Report: A 38-year-old woman had a fever and toothache 1.5 months before and had been treated for a dental abscess, which continued to fever, epistaxis, teeth out spontaneously, left Bell's Palsy, and swelling in the left side of her face. She had a history of immunosuppressive therapy and steroid-induced hyperglycemia for SLE. The PNS CT Scan found increased mucosal thickness of the left maxilla and sphenoid sinuses. Extensive debridement was done. Pathologic study of debrided samples showed coinfection of invasive mucormycosis and aspergillosis. She was treated with liposomal amphotericin B and voriconazole with complete recovery without recurrence after a one-year follow-up. Conclusion: In mucor and aspergillus coinfection, no one should be missed at first and treated by specific antifungal amphotericin B, with no time-wasting for a better prognosis. [ABSTRACT FROM AUTHOR]

Recently expanded reports of multidrug-resistant fungal infections underscore the need to develop new and more efficient methods for antifungal drug discovery. A ubiquitous problem in natural product drug discovery campaigns is the rediscovery of known compounds or their relatives; accordingly, we have integrated Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS) for structural dereplication and Yeast Chemical Genomics for bioprocess evaluation into a screening platform to identify such compounds early in the screening process. We identified 450 fractions inhibiting Candida albicans and the resistant strains of C. auris and C. glabrata among more than 40,000 natural product fractions. LC-MS/MS and chemical genomics were then used to identify those with known chemistry and mechanisms of action. The parallel deployment of these orthogonal methods improved the detection of unwanted compound classes over the methods applied individually. [ABSTRACT FROM AUTHOR]

Fungal periprosthetic joint infections (PJIs) are rare but increasingly recognized complications following total joint arthroplasty (TJA). While Candida albicans remains the most common pathogen, non-albicans Candida species and other fungi, such as Aspergillus, have gained prominence. These infections often present with subtle clinical features and affect patients with significant comorbidities or immunosuppression. Compared to bacterial PJIs, fungal infections pose unique diagnostic and therapeutic challenges, including biofilm formation, limited antifungal susceptibility, and protracted treatment courses. This narrative review synthesizes current evidence from research articles and review/metanalysis papers, focusing on fungal PJIs. The literature search encompassed publications from 2015 to 2024, identifying key insights on epidemiology, risk factors, microbiological profiles, diagnostic methods, therapeutic strategies, and outcomes. Both classical references and recent studies addressing emerging diagnostic biomarkers and biofilm-active therapies were included. It was shown that C. albicans remains the primary fungal pathogen in PJIs but non-albicans Candida species and other fungi are associated with more complex clinical scenarios, higher recurrence rates, and reduced infection-free survival. Patients commonly exhibit multiple comorbidities, compromised immune status, and previous prosthetic revisions. Diagnosis is complicated by slow-growing organisms and nonspecific inflammatory markers, prompting interest in novel diagnostics such as alpha-defensin, calprotectin, and next-generation sequencing. Two-stage revision arthroplasty, supplemented by prolonged targeted antifungal therapy, is considered the gold standard for chronic infections, although outcomes remain inferior to bacterial PJIs. Emerging strategies, including antifungal-impregnated beads and biofilm-disrupting agents, may improve local infection control. In conclusion, fungal PJIs constitute a challenging clinical entity demanding tailored diagnostic and therapeutic approaches. Further research into standardized diagnostic criteria, optimized antifungal regimens, biomarker validation, and refined surgical strategies is essential. Multidisciplinary collaboration, enhanced patient optimization, and innovative biofilm-directed therapies hold promise for improving outcomes and reducing the burden of fungal PJIs. [ABSTRACT FROM AUTHOR]

Fusarium head blight, caused by Fusarium graminearum, continues to be one of the most important and devastating fungal diseases on cereal grains including wheat, barley, and oat crops. F. graminearum produces toxic secondary metabolites that include trichothecene type A and type B mycotoxins. There are many variants of these toxins that are produced, and in the early 2010s, a novel type A trichothecene mycotoxin known as 3ANX (7-α hydroxy,15-deacetylcalonectrin) and its deacetylated product NX (7-α hydroxy, 3,15-dideacetylcalonectrin) were identified in Minnesota, USA. In the current study, a total of 31,500 wheat spikes over a period of 6 years (2015–2020) within Manitoba, Canada, were screened for the F. graminearum pathogen, which accounted for 72.8% (2015), 98.3% (2016), 71.9% (2017), 74.4% (2018), 92.6% (2019), and 66.1% (2020) of isolations. A total of 303 F. graminearum isolates, confirmed through sequencing of the ribosomal intergenic spacer, were further investigated for variation in the gene Tri1, which was previously associated with the production of the NX toxin, as well as the accumulation of mycotoxins. A subset of these isolates, consisting of 73 isolates, which tested positive or negative for the NX-Tri1-F/R assay in this study, were cultured in vitro using rice media. Mycotoxins were quantified in these samples using mass spectrometry. Using the same rice culture, genomic DNA was isolated, and the Tri1 coding sequence along with its flanking regions (upstream and downstream of the Tri1 gene) was amplified and sequenced. Deoxynivalenol (DON) accumulated in 96% of the cultures from these isolates, while 3-acetyl deoxynivalenol (3ADON) and 3ANX mycotoxins accumulated in 66% and 63%, respectively. Nivalenol, 15-acetyl deoxynivalenol, and NX mycotoxins were detected in 62%, 36%, and 19% of samples, respectively. A significant correlation was observed between 3ADON and 3ANX (r2 = 0.87), as well as between DON and 3ANX (r2 = 0.89). This study highlights the first large identification of 3ANX- and NX-producing isolates of F. graminearum in Western Canada. In addition, it is the first identification of 15ADON chemotypes producing 3ANX in Western Canada and the first identification of 3ANX and NX-producing isolates in Manitoba, collected from wheat samples. [ABSTRACT FROM AUTHOR]

The development of resistance to traditional antifungal therapies has necessitated the exploration of alternative treatment strategies to effectively manage fungal infections, particularly those induced by Candida albicans (C. albicans). This research investigates the possibility of integrating silver nanoparticles (AgNPs) with Terbinafine to improve antifungal effectiveness. Terbinafine, while potent, faces challenges with specific fungal strains, highlighting the need for strategies to enhance its treatment efficacy. Silver nanoparticles were produced through a light-activated, gelatin-based method, resulting in particle sizes ranging from 56.8 nm to 66.2 nm, confirmed by dynamic light scattering and scanning electron microscopy. Stability studies indicated that AgNPs produced with 30 mg of silver nitrate (AgNO₃) exhibited the greatest stability over 60 days across different temperature conditions. The analysis through UV-visible spectrophotometry revealed a notable shift in the absorption spectra as AgNO₃ concentrations increased, which was associated with a strengthening of plasmon resonance. The effectiveness of the AgNPs and Terbinafine combination was assessed against three strains of C. albicans (ATCC 10231, ATCC 90028, and ATCC 18804). Terbinafine demonstrated strong antifungal properties with minimum inhibitory concentrations (MIC) values ranging from 2–4 µg/mL, whereas AgNPs on their own displayed moderate effectiveness. The integrated formulation notably enhanced effectiveness, especially against strain ATCC 90028, revealing a synergistic effect (FIFi = 0.369). These results were complemented by the findings of the time-to-kill assay, where the same strain showed a 3.2 log₁₀ CFU/mL decrease in viable cell count. The process by which AgNPs boost activity entails the disruption of the fungal cell membrane and its internal components, probably as a result of silver ion release and the generation of free radicals. The results indicate that the combination of Terbinafine and AgNPs may act as a powerful alternative for addressing resistant fungal infections, presenting an encouraging direction for future antifungal treatments. [ABSTRACT FROM AUTHOR]

The red blood cell (RBC) membrane is unique and crucial for maintaining structural–functional relationships. Maternal smoking induces significant changes in the morphological, rheological, and functional parameters of both maternal and foetal RBCs, mainly due to the continuous generation of the free radicals. The major aim of this study was to follow the consequences of a secondary stressor, like fungal infection, on the already compromised RBC populations. The impact of Candida infection, a growing health concern, was investigated on four blood sample groups: mothers and their neonates originating from non-smoking versus smoking populations. Here, we searched for phenotypical and molecular markers that precisely reflected the effect of Candida infection on the RBC membrane; this included the level of hemolysis, appearance of morphological variants, formation of the lipid peroxidation marker 4-hydroxyl-nonenal, arrangement of the Band 3 molecules and activation of the Caspase 3. In most of the examined cases, the fungal infection increased the adverse symptoms induced by smoking, indicating a general stress response, likely due to an altered redox state of the cells. However, we were able to identify an atypical phenotype (clustered populations with shrinkage and membrane blebbing) in both the non-smoking and smoking populations, which might be a unique marker for Candida spp. infection. [ABSTRACT FROM AUTHOR]

Eumycetoma, a chronic fungal infection caused by Madurella mycetomatis, is a neglected tropical disease characterized by tumor-like growths that can lead to permanent disability and deformities if untreated. Predominantly affecting regions in Africa, South America, and Asia, it imposes significant physical, social, and economic burdens. Current treatments, including antifungal drugs like itraconazole, often show variable efficacy, with severe cases necessitating surgical intervention or amputation. Drug discovery for eumycetoma faces challenges due to limited understanding of the disease's molecular mechanisms and the lack of 3D structures for key targets such as Madurella mycetomatis CYP51, a well-known target for azoles' antifungal agents. To address these challenges, this study employed computational approaches, including homology modeling, virtual screening, free energy calculations, and molecular dynamics simulations, to repurpose FDA-approved drugs as potential treatments for eumycetoma targeting Madurella mycetomatis CYP51. To this end, a library of 2619 FDA-approved drugs was screened, identifying three promising candidates: montelukast, vilanterol, and lidoflazine. These compounds demonstrated favorable binding affinities, strong interactions with critical residues of the homology model of Madurella mycetomatis CYP51, and stability in molecular dynamics simulations, offering potential for further investigation as effective therapeutic options for eumycetoma. [ABSTRACT FROM AUTHOR]

Invasive aspergillosis (IA) is a fungal infection, which has traditionally been associated with neutropenia and immunosuppressive therapies. Our understanding of invasive aspergillosis has been evolving and, in the past few decades, IA among ICU patients has been recognized as a common infection and has become more widely recognized. The diagnosis and management of invasive aspergillosis in the ICU is particularly challenging, due to the unstable clinical condition of the patients, lack of diagnostic markers, increased risk of further clinical deterioration, multiple comorbidities, and a need for early assessment and treatment. In this article, we will discuss the challenges and pitfalls of the diagnosis and management of invasive aspergillosis in an ICU setting, along with a review of the current literature that is pertinent and specific to this population. [ABSTRACT FROM AUTHOR]

Fungal infections have become a growing concern in healthcare, particularly in immunocompromised individuals, with species like Candida, Cryptococcus, and Sporothrix posing significant challenges due to rising resistance and limited treatment options. In response, novel antifungal agents are being explored, including thiazolyl hydrazones. This study focuses on the development of a novel thiazolylhydrazone derivative, RW3. RW3 was synthesized to improve its water solubility and pharmacokinetic properties. The compound demonstrated a broad antifungal spectrum, particularly effective against Cryptococcus neoformans and Candida auris, with minimal irritant potential and low cytotoxicity. RW3 showed favorable solubility and high intestinal permeability, indicating potential for oral administration. The results suggest RW3 as a promising lead for further development as a therapeutic agent for systemic fungal infections. These findings underscore the importance of optimizing drug properties to enhance efficacy and safety profiles, opening the path for the development of innovative antifungal treatments. [ABSTRACT FROM AUTHOR]

Cryptococcosis is a fungal disease in humans and animals, caused by the Cryptococcus neoformans and Cryptococcus gattii species complexes. Clinical cryptococcosis primarily manifests as upper respiratory tract disease; however, dissemination to other organs, particularly the brain, can occur. Nasal colonisation and subclinical cryptococcosis are common in koalas (Phascolarctos cinereus) due to their shared environmental niche with Cryptococcus: Eucalyptus trees. However, for reasons that remain unclear, the prevalence of clinical disease is low in koalas. Interactions between respiratory pathogens and the nasal mycobiome are thought to play a role in the development and progression of numerous respiratory diseases. As such, this study aimed to characterise the mycobiome of the nasal vestibule in koalas with and without evidence of cryptococcal colonisation and subclinical disease via the next-generation sequencing (NGS) of the ITS1 region of the fungal internal transcribed spacer (ITS) gene. Samples were collected from 47 koalas from a population of free-ranging koalas in the Liverpool Plains, NSW, Australia, with a known history of Cryptococcus exposure and nasal colonisation. Of the 47 animals tested, 6.4% were culture-positive only, 4.3% were seropositive only, and 2.1% were culture- and seropositive. C. gattii was detected in four samples via NGS. C. neoformans was not detected via NGS. There were no significant differences in the nasal mycobiomes of Cryptococcus-positive and -negative animals; thus, we could not establish a definitive association between the mycobiome and infection outcomes. We identified a number of fungal genera that were significantly more abundant in samples from Cryptococcus-positive animals, but there was no apparent relationship between these genera and the development of cryptococcosis. This study represents the first investigation of the nasal mycobiota of wild koalas. Further studies involving koalas with clinical disease are necessary to determine the role of the nasal mycobiota in the development of cryptococcosis. [ABSTRACT FROM AUTHOR]

Microsporum canis, a zoophilic dermatophyte, infects the stratum corneum and keratinized tissues like hair and nails in cats and dogs, with cats serving as the primary reservoir. Most human infections arise from animal contact. We present the case of a girl aged 8 with skin scalp lesions persisting for two months. Several scalp lesions, with a maximum diameter of 4 cm, presented as erythematous plaques with superficial scaling, yellow crusts, and edematous areas with purulent exudate. Dermoscopy revealed yellow crusts on an erythematous background, along with white scales, pustules, broken hairs, and comma hairs. Ultraviolent-enhanced fluorescence dermoscopy (UEFD) showed slight celadon green fluorescence, which enhanced the diagnosis and further helped to monitor the treatment. The PCR test confirmed the presence of M. canis. Treatment included topical ciclopirox and oral terbinafine. Lesions on the scalp and noticeable hair regrowth were observed in the areas of hair loss after two months. Kerion celsi can result in severe alopecia. To prevent scarring associated with hair loss in children, early mycological diagnostics, supported by dermoscopy and UEFD, is recommended. [ABSTRACT FROM AUTHOR]

Fungal infections are common in highly immunosuppressed, solid organ transplant recipients. They can be quite difficult to diagnose in a timely manner; thus, we present a review of current studies focusing on broad categories of molecular diagnostics, i.e., metagenomic sequencing, magnetic resonance, and gas chromatography mass spectrometry. We further discuss their syndrome-specific utilization in the diagnosis of fungemia and disseminated disease, pneumonia, and central nervous system infections. We assess the level of evidence of their utility as fungal diagnostics particularly in solid organ transplant recipients using the STARD criteria. In addition, we provide future research directions to substantiate and appropriately utilize these platforms in clinical practice. Directed polymerase chain reaction testing and targeted metagenomic sequencing are being used clinically and show the most promise, though only in conjunction with conventional methods at this time. The majority of these platforms contain limited data, and thus further larger studies are needed in order to properly implement their use. [ABSTRACT FROM AUTHOR]