Medical mycology最新文献

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.

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.

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.

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.

Central nervous system mucormycosis (CNS-M) is a severe disease with difficult and often delayed diagnosis, leading to high mortality. The aim of this new study was to assess clinical and radiological presentation according to underlying conditions and dissemination routes to optimize diagnostic strategies. We conducted a retrospective national study including 54 CNS-M cases diagnosed between 2005 and 2020, with brain imaging reviewed by two neuroradiologists. CNS-M resulted from presumed hematogenous dissemination in 29 patients (54%) and from direct extension in 25 (46%), known as rhino-orbito-cerebral mucormycosis (ROCM). No neurological symptoms were found in 10/54 (19%), regardless of dissemination route. Hematogenous CNS-M mainly affected highly immunocompromised (HM or SOT) patients (90%), including 43% neutropenic. Radiology showed abscesses (87%) and small-vessel disease (39%). In ROCM, two patterns emerged depending on osteolysis (19/25, 76%) or its absence (6/25, 24%). ROCM without bone lysis, mostly in severely immunosuppressed patients, caused meningitis without abscess, whereas osteolytic ROCM led to abscess formation (11/18, 60%). Without osteolysis, perineural spread along the optic nerve occurred in 2/3 cases. Serum Mucorales PCR was positive in 91% of hematogenous and 64% of ROCM cases. Fungal co-infections occurred in 26%. This study underscores distinct invasion patterns and the need for extensive workup in CNS-M, highlighting the diagnostic value of MRI with gadolinium and serum Mucorales qPCR based on dissemination route and underlying condition. MRI is particularly useful in ROCM for detecting meningitis (80%), large-vessel disease (30%), and perineural involvement (8%).

Aspergillus fumigatus is a human pathogen and a ubiquitous environmental mould. Consequently, A. fumigatus may be exposed to agricultural fungicides widely used for crop protection. The use of azole fungicides in the environment has been implicated in the emergence of azole antifungal resistance in A. fumigatus. In vitro susceptibility of a collection of both clinical (n = 14) and environmental (n = 6) A. fumigatus isolates was determined against fungicides with different modes of action (demethylation inhibitors, Succinate DeHydrogenase Inhibitor (SDHI), Quinone outside Inhibitors (QoI), Methyl Benzimidazole Carbamate (MBC) and polyene). Sequencing of tubA, CYTB and SDHB, which encode the cellular targets of these fungicides, was performed. Eventually, the impact of resistance on the basal growth kinetics was assessed using a selection of two susceptible and two resistant isolates. Cross-resistance between medical triazole antifungal and agricultural triazole fungicides was confirmed, except for isolates with G54R/E substitutions in the cyp51A protein. No correlation was observed between resistance to triazole antifungals and imidazole fungicides. We identified seven MBC- (five environmental and two clinical isolates), five QoI- (three environmental and two clinical isolates) and one environmental SDHI-resistant isolates. Resistant phenotypes were associated with amino acid substitutions in beta-tubulin (F219Y and E217A), cytB (G143A) and sdhB (H270Y). Multi-fungicide resistance was not systematically associated with reduced growth kinetic. Multi-fungicide resistance, including at least resistance to one non-azole fungicide, was identified in sevenA. fumigatus isolates, of which two were clinical isolates. This last observation supports the hypothesis of the environmental pathway leading to antifungal resistance in A. fumigatus.

Chronic pulmonary aspergillosis (CPA) comprises a spectrum of lung disorders caused by ubiquitous fungi of the genus Aspergillus, with Aspergillus fumigatus being the most frequently identified pathogen. The disease is globally prevalent and associated with significant morbidity and mortality. Here, we investigated the species distribution, antifungal susceptibility and genetic relatedness of Aspergillus isolates from CPA patients and environmental sources in South India. All tested isolates were susceptible to common antifungals, and A. fumigatus was overall the most common species. Isolates from patients and the environment occasionally displayed identical genotypes, suggesting CPA patients acquire the disease from the environment.

LysM proteins are widely distributed in fungi of diverse lifestyles, including pathogens of humans and animals. Using bioinformatic methods, LysM proteins have been identified in representative yeasts of medical importance. However, LysM proteins have been found in only four ascomycete yeasts (Candida subhashii, C. tropicalis, Debaryomyces fabryi, and D. hansenii). In contrast, almost all basidiomycete yeasts contain at least one LysM effector but lack subgroup C chitinases. Notably, a unique LysM effector is highly conserved among all the lipid-dependent Malassezia species. The repertoire of LysM proteins in medically important yeasts appears to be more determined by the fungal lifestyle than by host colonization.

Candidemia is a common healthcare-associated infection associated with substantial morbidity and mortality. Candida parapsilosis is among the most common causative species; it has a notable ability to form biofilms and colonize skin, facilitating patient-to-patient spread, and it is increasingly associated with fluconazole resistance. We aimed to describe temporal trends, clinical characteristics, and antifungal resistance patterns among C. parapsilosis candidemia hospitalizations in the United States during 2016-2024. We used the Premier Healthcare Database (which represents >500 hospitals contributing laboratory data) to identify hospitalizations with ≥1 blood culture positive for C. parapsilosis. We calculated rates of C. parapsilosis candidemia hospitalizations and described characteristics overall and stratified by time period (2016-2019, 2020-2021, 2022-2024). We also compared characteristics of hospitalizations with vs. without fluconazole resistance. Among 1943 C. parapsilosis candidemia hospitalizations, prevalence peaked during the COVID-19 pandemic (10.4 per 100 000 hospitalizations in 2020-2021) and was highest among adults aged 45-64 years, male patients, and non-Hispanic Black patients. Many hospitalizations involved intensive care unit admission (67%), central venous catheter use (51%), and mechanical ventilation (37%). Fluconazole resistance rates increased from 3.1% in 2016-2019 to 11.7% in 2022-2024. In-hospital death or discharge to hospice was more frequent among hospitalizations involving fluconazole-resistant isolates vs. those without fluconazole-resistant isolates (42% vs. 28%, P = .017). Increased fluconazole resistance in C. parapsilosis is a growing public health concern. Surveillance, infection prevention and control practices, and routine antifungal susceptibility testing are essential to inform clinical management and public health strategies.