Medical mycology最新文献

{"title":"Host receptor-mediated responses to Candida albicans: An update.","authors":"Hanyu Zhu, Xue Wang, Jing Shao","doi":"10.1093/mmy/myag111","DOIUrl":"https://doi.org/10.1093/mmy/myag111","url":null,"abstract":"<p><p>Candida albicans is a commonly encountered dimorphic fungus that normally resides in the human body. Once the host is immune-compromised or endures long-term antibiotic treatment, C. albicans will transform into an opportunistic pathogen that can cause from superficial mucosal diseases (e.g., oropharyngeal candidiasis) to life-threatening invasive infections (e.g., candidemia). Since the resistance rate of clinical C. albicans is rapidly increasing, there is an urgency to expand the current antifungal armamentarium. It has been shown that a growing body of host receptors can recognize the cell wall components of C. albicans (e.g., β-glucan, chitin and mannan), and trigger potent innate immune responses with enhanced phagocytosis, reactive oxygen species, and inflammatory cytokine production. In this review, we classify the host receptors into two categories: the receptors that directly interact with the epitopes of C. albicans, and those that act as co-receptors to aid in epitope recognition. The former receptors include Dectin-1/2/3, Mincle, MR, DC-SIGN, MBL, CR3, LYSMD3, NKp30 and SPINK7, whereas the latter ones consist of TLR2/4, EphA2/B2, galectin-3, gC1qR, AhR, EGFR and HER2. We not only characterize the antifungal modes of these host receptors during C. albicans infection, but also summarize the features underlying the recognition of C. albicans epitopes by these receptors. The advancements in PRRs can largely expand our scientific understanding of antifungal mechanisms, and lay a solid foundation for the development of new antifungal agents for the clinical treatment of systemic infections caused by C. albicans.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of suspected Candidozyma auris outbreaks in Malaysia using integrated genomic, clinical and antifungal susceptibility analyses (Investigation of Candidozyma auris outbreaks in Malaysia).","authors":"Xue Ting Tan, Joo Thye Cheng, Wei Xuan Tuang, Heng Gee Lee, Siti Noraihan Khamis, Nurulyumni Faraha Md Sharizam, Yii Ling Liow, Mohd Khairul Izzati Omar, Chui Yng Chong, Lee Lee Low","doi":"10.1093/mmy/myag109","DOIUrl":"https://doi.org/10.1093/mmy/myag109","url":null,"abstract":"<p><p>Candidozyma auris (formerly Candida auris) is an emerging multidrug-resistant fungus with limited genomic epidemiological data from Malaysia. This study investigated the genomic epidemiology, clinical characteristics and antifungal susceptibility of C. auris outbreak isolates using an integrated whole-genome sequencing (WGS) approach. Eleven clinical C. auris isolates from five healthcare facilities across three Malaysian states were analysed alongside clinical and epidemiological data. Antifungal susceptibility testing was performed for azoles, echinocandins, amphotericin B, flucytosine, and manogepix. Among 11 patients, seven had candidemia and four were colonized. Median age was 48 years, with diabetes mellitus, chronic kidney disease and hypertension as the most common comorbidities. All candidemia patients had urinary and central venous catheters; 71% required mechanical ventilation, 43% had haemodialysis and recent surgery respectively. Recent antibiotic exposure was common, whereas none had prior antifungal therapy. All isolates belonged to Clade I but separated into distinct genomic clusters, supporting healthcare-associated transmission within clusters and simultaneous circulation of multiple genomic groups. All Johor-associated isolates were fluconazole resistant and carried ERG11 K143R and CDR1 V704L substitutions. An ERG5 variant was detected in non-Johor isolates with amphotericin B MICs ≥1µg/ml. The MICs for other antifungals remained low across isolates. Echinocandin therapy was initiated in 27% of patients, with one survivor. Our C. auris showed genomic diversity, distinct healthcare-associated clustering and variable antifungal susceptibility. Integrating WGS with clinical and susceptibility data enhanced outbreak investigation of C. auris.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of a multiplex qPCR assay for rapid diagnosis of fungal pneumonia and tuberculosis in people with advanced HIV disease.","authors":"Thiago Brasil de Moura da Costa, Pedro Henrique Nascimento Theodoro, José Henrique de Melo Neto, Fernando Almeida-Silva, Maria Cristina Lourenço, Rodrigo Almeida-Paes, Andrea d'Ávila Freitas, Valdiléa G Veloso, Sandra Wagner Cardoso, Maria José Buitrago, Marcel de Souza Borges Quintana, Freddy Perez, Rosely Maria Zancopé-Oliveira","doi":"10.1093/mmy/myag108","DOIUrl":"https://doi.org/10.1093/mmy/myag108","url":null,"abstract":"<p><p>Fungal pneumonias and tuberculosis (TB) remain major causes of mortality among people living with advanced HIV disease (PLWHA). Their overlapping clinical manifestations delay diagnosis in developed and resource-limited settings, with greater impact where access to rapid diagnostic tools is limited. This study evaluated the performance of a multiplex quantitative PCR (qPCR) assay for simultaneous detection of Histoplasma capsulatum, Cryptococcus neoformans, Pneumocystis jirovecii, and Mycobacterium tuberculosis complex in respiratory samples from PLWHA. A cross-sectional study was conducted at the Instituto Nacional de Infectologia Evandro Chagas (Rio de Janeiro, Brazil) between December 2023 and March 2025. Adults with HIV infection (CD4 < 200 cells/mm³) and clinical or radiological evidence of pulmonary infection were enrolled. Standard diagnostic methods included culture, microscopy, antigen detection (CrAg-LFA, urinary Histoplasma antigen, TB-LAM), GeneXpert® MTB/RIF, and commercial qPCR for P. jirovecii. The multiplex assay targeted the ITS region (H. capsulatum and C. neoformans), mtLSU (P. jirovecii), and IS6110 (M. tuberculosis). Among 198 screened participants, 88 met inclusion criteria (mean CD4 count: 56 cells/µL). Diagnosis included TB (56.8%), pneumocystosis (34.1%), histoplasmosis (10.2%), and cryptococcosis (11.4%); 25% presented coinfections. The multiplex qPCR showed 100% sensitivity for histoplasmosis, 80% for pneumocystosis, and 40% for both cryptococcosis and TB, with specificities ≥ 82% and 100% for TB. Overall accuracy ranged from 66% to 86%. Mortality was 12.5%, highest among cryptococcosis cases (20%). The assay provided accurate detection of H. capsulatum and P. jirovecii, although performance was limited for TB and cryptococcosis, supporting its use as a complementary molecular tool for differential diagnosis in PLWHA.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mucormycosis outbreak caused by Rhizomucor pusillus in a Hematopoietic Stem Cell Transplant Unit, Brazil.","authors":"Giovanni Luís Breda, Regielly Caroline Raimundo Cognialli, Bram Spruijtenburg, Eelco F J Meijer, Graziela Cristina Buzutti Canova, Vania Aparecida Vicente, Rafaella Muratori, Gisele Loth, Samir Kanaan Nabhan, Vaneuza Araújo Moreira Funke, Flávio Queiroz-Telles","doi":"10.1093/mmy/myag107","DOIUrl":"10.1093/mmy/myag107","url":null,"abstract":"<p><p>Mucormycosis is a severe fungal infection with high mortality in immunocompromised patients. Although most cases occur sporadically in the community setting, there are reports of healthcare-associated outbreaks of mucormycosis. We describe the investigation and clinical features of an outbreak of mucormycosis caused by Rhizomucor pusillus in a hematopoietic stem cell transplant (HSCT) unit in Brazil. Cases were screened through the hospital records, defined according to the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium criteria, and classified as HSCT unit-acquired or not. Mucormycosis incidence was monitored from 2 years before the index case until 2 years after the last case. The clinical course of identified cases and potential environmental exposure data were recorded. Microbiological samples were identified with conventional methods and internal transcribed spacer sequencing; whole genome sequencing was performed for phylogenetic analysis. Potential source investigation was conducted according to the US Centers for Disease Control recommendations. Four proven cases of HSCT-unit-acquired mucormycosis were identified over a 10-month period. Rhizomucor pusillus was identified in three of the four patients. Disseminated disease, beginning with pulmonary infection, was the most common clinical presentation. Survivors (75%) received treatment with lipid complex amphotericin B, isavuconazole, and/or surgical resection. Environmental investigation was negative and phylogenetic analysis demonstrated that isolates were not clonal. Following air system maintenance, no further cases were identified. We characterize the first reported outbreak investigation of mucormycosis caused by R. pusillus in a Brazilian HSCT unit, with favorable outcomes in most cases despite aggressive clinical presentation. Despite the lack of clonality and negative environmental investigation, epidemiological evidence strongly suggests nosocomial transmission.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential impact of glycemic control with Candida and dermatophyte infections among diabetic patients.","authors":"Maryam Salih, Mohammed Yawoz","doi":"10.1093/mmy/myag104","DOIUrl":"10.1093/mmy/myag104","url":null,"abstract":"<p><p>Diabetes mellitus (DM) is a significant risk factor for fungal infections, particularly Candida and dermatophytes, and glycemic control may be associated not only with the presence of these fungi but also the pattern of these infections. This study aimed to evaluate the relationship between glycemic control (HbA1c) and the type of fungal infection among diabetic patients. A cross-sectional study was conducted on 113 diabetic patients with suspected fungal infections. Clinical samples were collected from different body sites and analyzed using phenotypic and molecular methods. Patients were stratified according to glycemic control into good (HbA1c < 6.5%), poor (HbA1c 6.5%-7.9%), and very poor (HbA1c ≥ 8.0%) groups. A significant association was observed between glycemic control and the type of fungal infection (P = 0.015). Dermatophyte infections were more common in patients with good glycemic control (64.1%), while Candida infections increased with poorer glycemic control, reaching their highest prevalence in the very poor control group (83.3%). Dermatophytes were distributed across multiple anatomical sites, whereas Candida was mainly associated with moist and occluded areas. Overall, the interdigital region was the most affected site (37.5%). Candida infections were more common in female patients (20/33, 60.6%), while dermatophyte infections were more common among male patients (28/47, 59.6%). Furthermore, diabetes duration differed significantly across glycemic control groups. These findings demonstrate a significant association between glycemic control and the pattern of superficial fungal infections in diabetic patients. Poor glycemic control was associated with increased Candida infections, whereas dermatophyte infections were more frequent in better-controlled patients, highlighting the role of glycemic status in the distribution of fungal infections.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk factor analysis for early and late invasive Candida infections in solid organ transplant recipients.","authors":"Lilly Meyer, Jaromil Frossard, Peter W Schreiber, Oriol Manuel, Frederic Lamoth, Nina Khanna, Katia Boggian, Laura Walti, Christian Garzoni, Christian van Delden, Nicolas J Mueller, Dionysios Neofytos","doi":"10.1093/mmy/myag106","DOIUrl":"10.1093/mmy/myag106","url":null,"abstract":"<p><p>Contemporary data on risk factors for invasive candidiasis (IC) in solid organ transplant recipients (SOTr) are rare. This follow-up study on a large multicenter cohort study, nested within the Swiss Transplant Cohort Study, identifies risk factors for IC during the first year posttransplant. Among 4755 and 4519 SOTr identified between 0-3 months (early) and 4-12 months (late) posttransplant, 90 (1.9%) and 48 (1.1%) had 109 and 50 episodes of IC, respectively. Posttransplant Candida colonization (HR: 3.2; 95% CI: 1.67-6.14; P < .001), and posttransplant anastomosis (HR: 3.14; 95% CI: 1.74-5.69; P < .001) and bleeding/vascular complications (HR: 3.66; 95% CI: 2.38-5.62; P < .001) were independent risk factors for early IC, while transplantation between 2015 and 2020 (HR: 0.57; 95% CI: 0.38-0.88, P = .011) and male sex (HR: 0.63; 95% CI: 0.59-0.88; P = .026) demonstrated lower risk for early IC in multivariable analysis for all transplant types. Systemic antifungal prophylaxis (HR: 30.9; 95% CI: 4.9-194; Padj = .003) was associated with increased risk of early IC in kidney/kidney-pancreas recipients in univariable analysis. Posttransplant anastomosis (HR: 4.39; 95% CI: 2.49-7.72; Padj < .001) and surgical site/surgical other complications (HR: 3.62; 95% CI: 2.03-6.46; Padj < .001) were independent risk factors for late IC in univariable analysis for all transplant types. In conclusion, this study highlights the impact of posttransplant Candida colonization and posttransplant surgical complications on the occurrence of IC. These findings can support the design of more effective prophylactic strategies and inform clinical practice in this vulnerable patient population.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical management, antifungal susceptibility, and predictors of 28-day mortality in Candidozyma auris candidemia: A single-center cohort study.","authors":"Ayse Kaya, Hatice Rahmet Guner, Imran Hasanoglu, Fatma Eser, Aziz Bozkurt, Yesim Aybar Bilir, Muge Ayhan, Bedia Dinc, Bircan Kayaaslan","doi":"10.1093/mmy/myag105","DOIUrl":"10.1093/mmy/myag105","url":null,"abstract":"<p><p>Candidozyma auris (Candida auris) candidemia is a serious healthcare-associated infection with substantial mortality and limited treatment options. We retrospectively evaluated adult patients with C. auris candidemia at a tertiary care center between June 2022 and December 2025 to describe clinical management, microbiological outcomes, antifungal susceptibility, and factors associated with 28-day mortality. The descriptive cohort included 108 patients; mortality status was available for 107. Most patients (92.6%) were in intensive care at candidemia onset, and among evaluable patients, 76.1% had prior C. auris colonisation detected. Twenty-eight-day mortality was 41.1% (44/107). Non-survivors were older and had higher Charlson Comorbidity Index, Pitt bacteremia, and Sequential Organ Failure Assessment (SOFA) scores. Central venous catheter removal was more frequent among survivors (72.7% vs. 45.0%; P = .012), although removal timing and time to initiation of effective antifungal therapy did not differ significantly between groups. In multivariable analysis, Charlson Comorbidity Index (adjusted odds ratio [aOR], 1.22; 95% confidence interval [CI], 1.02-1.44) and SOFA score (aOR, 1.16; 95% CI, 1.05-1.27) were independently associated with 28-day mortality. Resistance rates were 95.1% for fluconazole, 31.2% for amphotericin B, and 1.3% for both anidulafungin and micafungin; multidrug resistance rate was 28.6%, and no isolate met the definition of pandrug resistance. Mortality in C. auris candidemia was mainly associated with baseline comorbidity burden and acute organ dysfunction. Local susceptibility surveillance and early recognition of high-risk patients may support treatment and infection-control strategies.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A pragmatic approach to investigating nosocomial acquisition of rare and emerging molds.","authors":"Aleksandra Marek, Fabianne Carlesse, Linda Bagrade, Eelco F J Meijer, Gordon Ramage, Anuradha Chowdhary, Juliëtte A Severin, Andreas Voss, Thomas J Walsh, Abhijit M Bal","doi":"10.1093/mmy/myag103","DOIUrl":"10.1093/mmy/myag103","url":null,"abstract":"<p><p>Invasive mold disease is associated with high mortality in immunosuppressed patients. While Aspergillus spp. and the Mucorales are well known, several other molds have emerged that cause infections and even outbreaks in susceptible hosts. These include Fusarium spp., Scedosporium spp., Lomentospora prolificans, and several others. The principles of preventing nosocomial mold infections include use of high-efficiency particulate air filters, removal of any potential sources of contamination, and risk-assessment of construction sites in adjacent areas. However, there is limited information on the approaches to assessment and management of outbreaks when there is a cluster of rare mold infections. The incubation period of rare and emerging molds is unknown and ascertaining whether the origin is nosocomial or community-acquired is difficult. Surveillance may be required to determine whether cases are part of an ongoing problem. The environmental niches of the rare molds are unique; e.g., Fusarium spp. are associated with hospital water distribution systems. They also cause outbreaks of fungal keratitis. Many rare molds are seen in cases of medicinal product contamination and managing such outbreaks requires support from and coordination by national agencies. Environmental precautions around patients and construction activities should be reassessed during outbreaks. A systematic approach is required when evaluating a cluster or even an isolated nosocomial case. Surveillance systems should be strengthened. This review summarizes the information available on outbreaks of rare and emerging molds. We further discuss a set of actions that may be undertaken in the event of an outbreak.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baseline fluconazole heteroresistance and risk of relapse within 6 months among patients with neurocryptococcosis in the Brazilian Amazon.","authors":"Izabela de Mesquita Bárcia Moreira, Ingrid Bianca Silva, João Flávio Dias do Val Bisneto, Naira Sulany Oliveira de Sousa, Juan Diego Ribeiro de Almeida, Robert Langlady Lira Rosas Filho, Nayara de Fátima Lazameth-Diniz, Katia Santana Cruz, Carla Silvana da Silva Santos, Ani Beatriz Jackisch Matsuura, Érica Simplício de Souza, Márcia de Souza Carvalho Melhem, Hagen Frickmann, João Vicente Braga de Souza","doi":"10.1093/mmy/myag102","DOIUrl":"10.1093/mmy/myag102","url":null,"abstract":"<p><p>Cryptococcosis is a severe systemic mycosis, and relapse may be influenced by fungal subpopulations that survive fluconazole exposure. This retrospective cohort study investigated whether fluconazole minimum inhibitory concentration (MIC) and the heteroresistant (HetR) phenotype of the first available diagnostic cerebrospinal-fluid isolate were associated with recorded relapse within 6 months in 70 patients with neurocryptococcosis from Amazonas, Brazil. One clinical isolate per patient, comprising 64 Cryptococcus neoformans molecular type VNI and 6 Cryptococcus gattii molecular type VGII isolates, was evaluated by broth microdilution and endpoint-based fluconazole heteroresistance level (HFL) testing. Using an operational criterion of HFL/MIC ≥ 8, corresponding to visible growth at least three twofold dilutions above the MIC, 43 of 70 isolates (61.4%) were classified as displaying a HetR phenotype. Six-month follow-up was available for 69 patients. Recorded relapse occurred in 12 of 42 patients infected with HetR isolates (28.6%) and in 4 of 27 patients infected with non-HetR isolates (14.8%). Although relapse was numerically more frequent in the HetR group, the association was not statistically significant (conditional odds ratio, 2.27; exact 95% confidence interval, 0.59-10.96; two-sided Fisher's exact test, P = .248). The HFL/MIC ratio also did not differ significantly according to recorded relapse status (P = .165). The HetR phenotype of the first available diagnostic isolate, defined operationally in this study as HFL/MIC ≥ 8, was frequent but was not significantly associated with recorded relapse within 6 months in this cohort.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new MRR1 gain-of-function mutation involved in cross-resistance to antifungal agents in the fungal priority pathogen Candida parapsilosis.","authors":"Manon Cadeau, José Rivaldo de Lima, Alina Marcela Sabou, Estelle Robert, Patrice Le Pape, Isabelle Ourliac-Garnier, Florent Morio","doi":"10.1093/mmy/myag094","DOIUrl":"10.1093/mmy/myag094","url":null,"abstract":"<p><strong>Objectives: </strong>Candida parapsilosis is a leading cause of invasive candidiasis globally, with rising reports of fluconazole resistance threatening its clinical management. Among the mechanisms involved, gain-of-function mutations in the MRR1 gene have emerged as key drivers of antifungal resistance. We aimed to investigate a novel amino acid substitution (G982E) in the Mrr1 zinc cluster transcription factor, identified in a fluconazole-resistant C. parapsilosis isolate from a patient exposed to fluconazole.</p><p><strong>Methods: </strong>Using CRISPR-Cas9 genome editing, we introduced the G982E variant into two fluconazole-susceptible C. parapsilosis genetic backgrounds. The antifungal susceptibility of the engineered mutants was assessed in vitro against a broad panel of systemic antifungal agents. A Galleria mellonella infection model was also used to evaluate the impact of the G982E variant on antifungal treatment efficacy and virulence in vivo.</p><p><strong>Results: </strong>Acquisition of the G982E substitution dramatically altered the antifungal susceptibility profile, particularly for fluconazole for which the minimum inhibitory concentration (MIC) increased to >256 µg/mL. However, the magnitude of the MIC increase varied by azole, with the greatest increase seen for fluconazole (>9-10 log-fold), followed by voriconazole (5 log-fold), isavuconazole (3 log-fold), but also flucytosine (1.5 log-fold). In contrast, susceptibility to posaconazole remained largely unchanged. In vivo, this new variant conferred fluconazole treatment failure but was associated with a significant reduction in virulence.</p><p><strong>Conclusions: </strong>The G982E is a novel Mrr1 gain-of-function mutation driving high-level fluconazole resistance in C. parapsilosis. These findings reinforce the central role of Mrr1 in antifungal resistance, underscore the functional diversity of its mutational landscape, with potential implications for fungal fitness and transcriptional regulation.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}