Medical mycology最新文献

Candida glabrata is a major fungal pathogen capable of causing life-threatening disseminated infections, especially in immunocompromised individuals. Oxygen levels vary widely across host niches, and hypoxia is increasingly recognized as a key modulator of fungal pathogenicity. However, how low-oxygen environments influence adhesion and virulence in C. glabrata remains poorly understood. Here, we investigated C. glabrata adhesion under rigorously controlled oxygen conditions using a sealed hypoxic workstation and identified genes responsible for hypoxia-induced adhesion. Adhesion to human epithelial and endothelial cells was significantly enhanced under hypoxic conditions. RNA-seq analysis revealed that among differentially expressed genes, the adhesin gene EPA6 was consistently upregulated under anaerobic conditions in multiple strains. Using gene deletion and complementation, we found that EPA6 is required for adhesion under hypoxia. Using three distinct in vivo models (intravenous infection, gastrointestinal colonization, and systemic dissemination from the gut), we showed that EPA6 was crucial for fungal burden and pathogenicity. Because the epa6Δ mutant had normal growth and stress tolerance, we consider that its attenuated virulence (reduced colonization and dissemination) resulted from reduced adhesion. This study provides the first demonstration of fungal adhesion under precisely monitored oxygen conditions that mimic those in host physiology. These findings demonstrate that hypoxia promotes C. glabrata adhesion and dissemination through EPA6, highlighting a key virulence mechanism.

Cryptococcal meningitis (CM) remains one of the leading causes of morbidity and mortality among people living with HIV, particularly in low and middle-income countries where access to standard antifungal therapy is limited. Despite global advances in HIV care, early diagnosis and effective treatment of cryptococcal disease continue to represent major challenges in resource-limited settings. We conducted a retrospective registry-based cohort study of HIV patients and a first episode of CM admitted to a Peruvian national referral hospital between 2005 and 2015. Cox proportional hazards models were used to identify independent variables related to 30- and 90-day mortality. A total of 83 patients were included, 87% were males with a median age (interquartile range) of 33.8 (28.7-45.1) years. At baseline, 27.7% of patients had received antiretroviral therapy. Mortality at 30 and 90 days was 26.5% and 31.3%, respectively. In multivariable Cox models, the limited sample availability (59 for baseline and 83 for treatment analyses), constrained the precision estimates; nevertheless, altered consciousness, hyponatremia, and headache as independent predictors of mortality [30-day Hazard Ratios (HR): 7.6 (2.2-26.0); 5.4 (1.6-18.2); 0.1 (0.02-0.4); and 90-day HR: 7.1 (2.0-26.0); 10.9 (2.8-41.8); 0.1 (0.02-0.4), respectively]. In treatment analyses, fluconazole monotherapy or the absence of antifungals were significantly associated with higher mortality [30-day HR: 2.7 (1.1-6.8); 21.1 (7.8-57.5) and 90-day HR: HR: 2.8 (1.1-7.3); 20.1 (7.4-54.5), respectively]. In resource-limited settings, mortality from HIV-associated CM remains unacceptably high. These findings underscore the urgent need to enhance early diagnostic strategies and ensure access to optimal antifungal therapy to improve survival outcomes.

This study evaluated squalene epoxidase (SQLE) mutations, and the antifungal susceptibility profile of Trichophyton species isolated from patients with recalcitrant dermatophytosis in Pakistan. The study was conducted at the Aga Khan University Hospital Laboratory, Karachi, between January 2023 and February 2024. Identification of the isolates was performed through sequencing of the internal transcribed spacer (ITS) region. Antifungal susceptibility testing for terbinafine, itraconazole, and voriconazole was performed using the broth microdilution method based on modified European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. Minimum inhibitory concentrations (MICs) were interpreted using EUCAST epidemiological cutoff values to classify isolates as wild-type or non-wild-type. DNA extraction was carried out using the QIAamp DNA Mini Kit, and ITS and SQLE gene regions were amplified and sequenced via Sanger sequencing. A total of 37 Trichophyton isolates were included, of which 17 (45.9%) were Trichophyton mentagrophytes, 16 (43.2%) were T. indotineae, 2 (5.40%) were T. rubrum, and 2 (5.40%) were T. interdigitale identified through ITS sequencing. Non-wild-type MICs to terbinafine were observed in 28 (75.7%) isolates, while eight isolates (21.6%) also showed non-wild-type MICs to itraconazole; no isolates demonstrated non-wild-type MICs to voriconazole. The most prevalent SQLE gene mutations were F397L (54%), Q408R (32.4%), and A448T (21.6%). This study represents the first report from Pakistan of antifungal resistance and SQLE gene mutations in Trichophyton strains from patients with recalcitrant dermatophytosis. The high prevalence of resistance underscores the urgent need for capacity building in antifungal susceptibility testing and highlights the importance of guiding appropriate treatment strategies to manage resistant dermatophytosis in the region effectively.

Tinea corporis and tinea cruris are common dermatophyte infections of increasing public health concern, yet national US data are limited. We estimated incidence, risk factors, and diagnostic and treatment practices among a large Medicaid-insured outpatient cohort. Among ∼6 800 000 enrollees, 54 108 were diagnosed with tinea corporis (79.1/10 000 person-years) and 8386 with tinea cruris (12.2/10 000 person-years). Tinea corporis primarily affected young children and Black patients, while tinea cruris was prevalent among middle-aged men. Overall, <10% received diagnostic testing, and 7%-10% were treated with combination antifungal-corticosteroid products, highlighting the opportunities to increase testing and promote judicious antifungal use amid emerging resistance.

Reptiles can host and potentially spread a wide range of microorganisms, yet the composition and zoonotic potential of their associated fungi remain poorly characterized. This study investigated the cutaneous mycobiota of free-ranging snakes sampled during the "Festa dei Serpari" in Cocullo, Italy, with a specific focus on yeasts and the detection of Ophidiomyces ophidiicola among filamentous fungi. A total of 143 snakes from four species (i.e., Elaphe quatuorlineata, Hierophis viridiflavus, Natrix helvetica, and Zamenis longissimus) were examined. Sterile swabs from healthy and lesioned skin were cultured and analyzed using molecular methods. Yeast isolates included Pichia kudriavzevii, Blastobotrys raffinosifermentans, Cryptococcus neoformans, and Debaryomyces spp. Overall, 64.24% of samples showed fungal growth, with yeasts accounting for 11.52% of positive cultures, while O. ophidiicola was not detected. These results highlight the diversity of yeast communities associated with snakes and emphasize the importance of monitoring O. ophidiicola and fungal pathogens of zoonotic concern to elucidate the role of reptiles as potential sentinels of emerging pathogens.

This report describes the first discovery in Costa Rica of a multidrug-resistant strain of Nakaseomyces glabratus (formerly Candida glabrata). The infection occurred in a 39-year-old man who had a complicated medical history, with repeated intra-abdominal infections, and eventually died from septic shock. Antifungal susceptibility testing was performed, and Illumina whole-genome sequencing was conducted to identify mutations associated with the resistance profile. Genomic analysis identified critical non-synonymous mutations in key resistance genes, linked to azole and echinocandin resistance. This case underscores the critical threat of antifungal resistance and highlights the importance of genomic surveillance in understanding resistance mechanisms to guide public health responses.

Disseminated histoplasmosis (DH) is a severe opportunistic infection in people living with HIV/AIDS (PLWHA). We aimed to identify predictors of in-hospital death among PLWHA with DH and to assess the prognostic value of novel biomarkers. A cohort study was conducted at the São José Hospital of Infectious Diseases in Fortaleza, Brazil (March 2023-December 2024). Sixty-one patients were included; 15 (24.6%) died during hospitalization. Mortality was strongly associated with peripheral blood detection of Histoplasma capsulatum (relative risk, RR = 5.05; 95% confidence interval, CI = 2.30-11.10). Several laboratory markers were also associated with death, including elevated C-reactive protein (CRP) (P = .001), aspartate aminotransferase (AST) (P = .005), direct bilirubin (P = .017), lactate dehydrogenase levels (P = .011), and hypocalcemia (P = .003). Severe complications-renal replacement therapy (RR = 11.25; 95% CI = 3.64-34.80), mechanical ventilation (RR = 16.82; 95% CI = 4.23-66.84), and shock (RR = 33.44; 95% CI = 4.75-235.72)-were also linked to death. In receiver operating characteristic curve analysis, CRP exhibited the highest predictive performance (area under the curve = 0.787; 95% CI = 0.638-0.935), whereas Angiopoietin-2 showed the highest specificity (0.93). In the multivariate model, AST retained a trend towards an independent association with death (hazard ratio = 1.141; 95% CI 0.983-1.327). DH mortality remains high due to late HIV diagnosis and advanced disease. Early recognition and timely antifungal therapy are essential to improve survival.

Candida glabrata has emerged as a leading cause of fungal infections worldwide, characterized by inherent antifungal resistance. While considerable attention has focused on conventional resistance mechanisms, the contribution of epigenetic regulation to C. glabrata pathogenicity remains incompletely understood. Here, we investigated the role of Ubp10, a histone H2B deubiquitinase, in C. glabrata stress adaptation and virulence. Deletion of UBP10 resulted in a substantial increase in H2B ubiquitination compared to the wild-type, indicating its predominant role in H2B deubiquitination. Phenotypic characterization revealed that ubp10 mutant exhibited impaired growth kinetics, mitochondrial dysfunction with elevated reactive oxygen species production, and altered morphogenetic responses, including enhanced agar invasion but reduced biofilm formation. Most notably, the ubp10 mutant displayed a distinctive antifungal susceptibility profile with increased resistance to azoles coupled with enhanced susceptibility to echinocandins, correlating with dysregulated expression of drug-response genes (ERG6, ERG11, CDR1, FKS1, and FKS2). Transcriptional analysis further demonstrated that key oxidative stress response genes (CTA1, SOD1, and GPX2) were downregulated under basal conditions but hyperactivated upon H₂O₂ exposure. In a murine model of systemic candidiasis, the ubp10 mutant was avirulent, with 100% host survival. These findings establish Ubp10 as an important epigenetic regulator involved in C. glabrata pathobiology, linking histone H2B deubiquitination to stress adaptation, drug resistance, and virulence phenotypes.

Background: Non-Aspergillus invasive mould infections (IMIs) are emerging in immunocompromised patients, and liver is the second most commonly organ transplanted worldwide.

Methods: We conducted a multicenter retrospective case-control (1:1) study of liver transplant (LT) recipients diagnosed with non-Aspergillus IMIs in France between January 2007 and December 2021.

Results: We identified 27/14 332 (0.18%) LT recipients with non-Aspergillus IMIs. Mucorales spp. (48%) were the most common pathogens, followed by Scedosporium spp. (14%), Fusarium spp. (14%), and other IMIs (25%). Lungs were the primary infection site, followed by soft tissues, abdomen, brain, sinuses, heart, and bone. Multivariate analysis showed that a Model for End-stage Liver Disease score > 20 prior to transplantation and primary antifungal prophylaxis (with echinocandins or fluconazole) tended to increase the risk of non-Aspergillus IMIs by nearly threefold ((adjusted Odd Ratio (aOR): 3.73, 95% Confidence Interval (CI) [0.90-15.45], P = .07) and (aOR: 3.93; 95% CI [0.94-16.42], P = .06), respectively). The 6-month mortality rate was 55%. In a Cox survival model, non-Aspergillus IMIs were associated with a threefold increase in mortality risk (Hazard Ratio (HR) : 3.82 [2.01-7.26] P < .001).

Conclusion: Non-Aspergillus IMIs are rare but highly fatal infections whose early diagnosis in high-risk liver-transplanted patients is essential. Whether or not recently available molecular tools for diagnosing non-Aspergillus IMIs will improve their prognosis in the liver transplantation setting remains to be studied.

Phaeohyphomycoses (PHM), infections caused by pigmented fungi, are increasingly reported in kidney transplant recipients (KTR), but data remains scarce. We retrospectively reviewed all episodes of PHM in KTR at the Guadeloupe University Hospital (French West Indies) from January 1st, 2012, to December 31st, 2022. Eighteen episodes of PHM occurred in 17 KTRs, corresponding to an incidence of 1.56 cases per 100 person-years. Median time from transplantation to PHM onset was 15 months (interquartile range: 9.0-23.5 months). Most episodes were localized cutaneous infections (n = 16/18). Twelve fungal species were identified; Paraconiothyrium cyclothyrioides was the most frequent (n = 6/18, 33%). This fungus it is not yet acknowledged as pathogenic in the current European guidelines. Surgery was performed in 41% of episodes with available data-some data are missing due to the loss of paper files. Eighty-two percent of patients received antifungal therapy (mainly azoles). Overall outcome was favorable in 82%. Three deaths occurred during follow-up; one was directly attributable to disseminated PHM. Diagnosing PHM is not that unusual in this caribbean transplant center, mainly presented as localized skin infections, with a distinctive species distribution characterized by predominance of P. cyclothyrioides and absence of Alternaria spp. With accurate diagnosis, combine surgical/medical therapy and control of transplant organ management, the vast majority of patients can be successfully managed.