Journal de mycologie medicale最新文献

{"title":"Seborrheic dermatitis and dandruff: An overview of pathogenesis, role of Malassezia spp., and natural treatment approaches","authors":"Imrose Wasim ,&nbsp;Nur Shaid Mondal ,&nbsp;Joyjeet Dey ,&nbsp;Lunasmrita Saikia ,&nbsp;Douglas Law ,&nbsp;Saikat Sen ,&nbsp;Manish Kumar Gautam ,&nbsp;Partha Pratim Dutta","doi":"10.1016/j.mycmed.2026.101604","DOIUrl":"10.1016/j.mycmed.2026.101604","url":null,"abstract":"<div><div>Seborrheic Dermatitis (SD) and dandruff are prevalent dermatological disorders that primarily affect the sebaceous glands and have significant implications for adults and children. While chronic skin lesions characterise SD, dandruff is characterised by excessive scalp flaking, pruritus, and erythema. Despite their overlapping clinical manifestations, these conditions differ in their underlying pathophysiology, with overgrowth of Malassezia species (spp.) emerging as a central pathogenic factor in both. Malassezia, a commensal yeast naturally residing on the skin, has been implicated in exacerbating inflammation and triggering immune responses, thereby contributing to the initiation and progression of SD and dandruff. In this comprehensive review, we systematically evaluated the role of natural and plant-derived ingredients in managing SD and dandruff, with a particular focus on their effects on <em>Malassezia</em> spp. The literature search was conducted using Google Scholar, Google Patents, PubMed, and SciFinder until December 2025. The extracted data were qualitatively synthesised to identify key findings and highlight existing research gaps. The results indicate that <em>Malassezia</em> spp., particularly <em>Malassezia furfur</em>, play a pivotal role in SD and dandruff by overgrowing, leading to excessive sebum production, yeast colonisation, and subsequent inflammation. M. furfur has been shown to stimulate the release of proinflammatory cytokines and activate the NLRP3 inflammasome, further promoting the inflammatory cascade associated with these conditions. Plant-derived ingredients, such as antimicrobial and anti-fungal compounds, have garnered attention for their potential therapeutic effects. Several studies suggest that substances like tea tree oil, aloe vera and various herbal extracts may reduce <em>Malassezia</em> load and mitigate the inflammation associated with these disorders. However, there remains a lack of clarity regarding the precise mechanisms by which these natural agents influence the skin's microbiome and immune system. Further clinical investigations are essential to assess the efficacy, safety, and optimal formulations of these plant-based treatments. Despite promising evidence supporting their use, additional well-designed studies are needed to clarify their roles and to establish standardised treatment protocols for SD and dandruff management.</div></div>","PeriodicalId":14824,"journal":{"name":"Journal de mycologie medicale","volume":"36 1","pages":"Article 101604"},"PeriodicalIF":1.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146090456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Yeast Spectrum and antifungal susceptibility in a Hospital in Southwestern China: A retrospective Study (2020–2024)","authors":"Zhenzhen Wang,&nbsp;Lijuan Xiong,&nbsp;Kai Ma,&nbsp;Juan Liu,&nbsp;Kai Feng,&nbsp;Peng Yang","doi":"10.1016/j.mycmed.2025.101597","DOIUrl":"10.1016/j.mycmed.2025.101597","url":null,"abstract":"<div><div>The purpose of this study was to investigate the etiological spectrum of yeast isolates and the sensitivity to antifungal drugs in our hospital, both during and after the COVID-19 pandemic. A retrospective analysis was conducted from Jan 2020 to Dec 2024, focusing on the results of fungal culture and identification from specimens in our hospital. For the genus <em>Candida</em>, the sensitivity to several antifungal drugs was assessed using the microdilution method (ATB Fungus 3). During the five-y study period, a total of 5776 fungal strains were identified, with <em>Candida</em> species being the most common. Antifungal susceptibility tests revealed differences in the sensitivity of <em>Candida</em> species to various antifungal drugs. Specifically, <em>Candida</em> species exhibited higher sensitivity to amphotericin B, while their sensitivity to itraconazole was relatively lower. <em>C. albicans</em> showed a <strong>temporary increase</strong> in resistance to certain antifungals (e.g., voriconazole and itraconazole) during 2022–2023, this trend <strong>was not sustained</strong> in 2024. While the fluctuation in resistance trends of non - <em>albicans</em> Candida species is normal. In conclusion, the changing resistance patterns and underlying mechanisms of <em>Candida albicans</em> warrant close attention. More caution should be exercised in selecting appropriate drugs for the clinical treatment of <em>Candida</em> species.</div></div>","PeriodicalId":14824,"journal":{"name":"Journal de mycologie medicale","volume":"36 1","pages":"Article 101597"},"PeriodicalIF":1.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term treatment outcomes among AIDS patients with and without talaromycosis: A retrospective study","authors":"Dandan Gong ,&nbsp;Weiyin Lin ,&nbsp;Yaozu He ,&nbsp;Huihua Zhang ,&nbsp;Heping Zhao ,&nbsp;Shaozhen Chen ,&nbsp;Xuemei Ling ,&nbsp;Pengle Guo ,&nbsp;Xiaoping Tang ,&nbsp;Linghua Li","doi":"10.1016/j.mycmed.2025.101599","DOIUrl":"10.1016/j.mycmed.2025.101599","url":null,"abstract":"<div><h3>Objective</h3><div>To compare the long-term outcomes among AIDS patients with and without talaromycosis following initiation of antiretroviral therapy (ART).</div></div><div><h3>Methods</h3><div>This retrospective study included ART-naïve AIDS patients hospitalized at Guangzhou Eighth People's Hospital between January 1 and December 31, 2018. During the study period, ART was initiated in all patients per the standard of care. Virological outcomes, immunological responses, and mortality rates were assessed over the following five years.</div></div><div><h3>Results</h3><div>A total of 299 patients were included and 96 (32.1 %) were infected with <em>Talaromyces marneffei</em>. At baseline, patients with talaromycosis had a significantly lower CD4⁺ count (12.0 cells/μL vs. 41.0 cells/μL) and CD4⁺/CD8⁺ ratio (0.06 vs. 0.10) (all <em>P</em> &lt; 0.01). By 60 months, the CD4⁺ count had significantly increased to 370.0 cells/μL in the talaromycosis group and to 427.5 cells/μL in the non-talaromycosis group. The CD4⁺/CD8⁺ ratio improved to 0.53 and 0.56. The incidence of immune non-responders (INRs) during 24–60 months of follow-up in the two groups were 66.7 % vs. 55.4 %, 58.0 % vs. 50.6 %, 56.9 % vs. 47.6 %, 46.8 % vs. 40.5 %, 43.8 % vs. 32.9 %, 42.6 % vs. 29.2 %, 39.1 % vs. 31.1 %, respectively. Generally, differences in immune reconstitution were evident during the first 24 months but became non-significant between 30 and 60 months. The rates of viral suppression in the non-talaromycosis and talaromycosis groups during the five-year follow-up were 77.0 % vs. 71.0 %, 92.9 % vs. 91.2 %, 92.7 % vs. 86.3 %, 94.9 % vs. 90.0 %, 90.8 % vs. 93.6 %, respectively, and were comparable between the two groups (<em>P</em> = 0.18, 0.96, 0.37, 0.47, and 0.83). Similarly, the cumulative mortality did not differ significantly (11.3 % vs. 15.0 %, <em>P</em> = 0.345).</div></div><div><h3>Conclusion</h3><div>ART has a sustained impact on immune reconstitution, and the long-term outcomes of AIDS patients with talaromycosis are not inferior to those without talaromycosis. Therefore, timely ART is critical for improving prognosis of AIDS patients with talaromycosis.</div></div>","PeriodicalId":14824,"journal":{"name":"Journal de mycologie medicale","volume":"36 1","pages":"Article 101599"},"PeriodicalIF":1.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probable disseminated cryptococcosis relapse in a patient with Hodgkin's lymphoma treated with induction therapy resumption and autologous stem cell transplant","authors":"Hugo Bes-Berlandier ,&nbsp;Jan Patrick Stellmann ,&nbsp;Simar Berro ,&nbsp;Bachra Choufi ,&nbsp;Claudine Sohn ,&nbsp;Pierre Berger ,&nbsp;Jean Marc Schiano ,&nbsp;Angela Granata ,&nbsp;Faezeh Legrand ,&nbsp;Guenièvre Imbert ,&nbsp;Océane Marchand ,&nbsp;Zeina Sabouni ,&nbsp;Anthéa Deschamps ,&nbsp;Caroline Solas ,&nbsp;Romain Guilhaumou ,&nbsp;Prithvi Ramtohul ,&nbsp;Estelle Menu ,&nbsp;Coralie L’ollivier ,&nbsp;Stephane Ranque ,&nbsp;Jacques Sevestre","doi":"10.1016/j.mycmed.2026.101603","DOIUrl":"10.1016/j.mycmed.2026.101603","url":null,"abstract":"<div><div><em>Cryptococcus</em> species are fungi that primarily cause infections in immunocompromised patients. In cases of hematologic malignancies, it can result in central nervous system and disseminated infections which are associated with high morbidity and case-fatality rate. We present the case of a patient with Hodgkin's lymphoma who experienced a probable relapse in disseminated cryptococcosis during the consolidation phase of treatment. After prolonged induction therapy with amphotericin B and flucytosine, followed by isavuconazole maintenance, the patient achieved a favourable outcome. Six months after relapse of cryptococcosis, the patient underwent autologous stem cell transplantation (ASCT), which resulted in sustained lymphoma remission. The cryptococcosis was successfully contained. This case highlights the need for clinicians to consider reintroducing IT in patients who experience clinical and radiological worsening during the consolidation phase. The patient demonstrated sustained clinical and radiological improvement at seven months post-ASCT, notwithstanding the presence of active cryptococcosis. This suggests that ASCT appears to be safe and feasible when the prognosis of the underlying hematological malignancy warrants its use.</div></div>","PeriodicalId":14824,"journal":{"name":"Journal de mycologie medicale","volume":"36 1","pages":"Article 101603"},"PeriodicalIF":1.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro Susceptibilities to caspofungin of Candida spp. isolated from the Polyvalent Intensive Care Unit of Fattouma Bourguiba University Hospital: First report of resistant mutants in Tunisia","authors":"Sameh Belgacem ,&nbsp;Wissal Chebil ,&nbsp;Ichrak Ferjani ,&nbsp;Donia Ghedira ,&nbsp;Maha Mastouri ,&nbsp;Hamouda Babba","doi":"10.1016/j.mycmed.2026.101601","DOIUrl":"10.1016/j.mycmed.2026.101601","url":null,"abstract":"<div><h3>Introduction</h3><div><em>Candida</em> infections are becoming increasingly common in the Intensive Care Unit (ICU) setting representing a real threat to compromised patients. Echinocandins are considered the first-line treatment for the management of these infections. This work aimed to study the susceptibility of <em>Candida</em> species involved in invasive fungal infections at the ICU department of the University Hospital Fattouma Bourguiba of Monastir to caspofungin and evaluate the effect of overuse of this antifungal agent on the evolution of Minimal Inhibitory Concentrations (MICs).</div></div><div><h3>Materials and methods</h3><div>This study concerned 269 <em>Candida spp.</em> strains isolated from 152 patients of the ICU from January 2018 to May 2021. The MICs were determined according to the Clinical and Laboratory Standards Institute (CLSI) reference method. The strains categorized as resistant were sequenced at the Hot Spot (HS) region of the FKS gene. Additionally, the relationship between MICs and monthly caspofungin consumption at the ICU department was evaluated using SPSS software.</div></div><div><h3>Results</h3><div><em>Candida albicans</em> was the most prevalent species representing 44 % (119/269), followed by <em>C. tropicalis</em> (52/269) and <em>C. glabrata</em> (51/269) (19 % each). A total of 223 isolates were subjected to susceptibility testing. Resistance to caspofungin was detected in 13 <em>C. glabrata</em> isolates (5.8 %). That is to say, in total, 30 % of the tested <em>C. glabrata</em> isolates were categorized as resistant based on their MIC values However, only one strain exhibiting a cross-resistance to anidulafungin, carried a mutation in the HS region of the FKS1 gene underscoring a discrepancy between phenotypic and genetic resistance. The evolution of MIC values was significantly correlated with caspofungin consumption for <em>C. albicans</em> and <em>C. tropicalis</em> species however non-significant for <em>C. glabrata</em> and the remaining species.</div></div><div><h3>Conclusion</h3><div>To prevent the rise of resistance to caspofungin, it is necessary to improve mycological surveillance by elaborating breakpoint values adapted to the local fungal ecology and to rationalize the prescription of this molecule.</div></div>","PeriodicalId":14824,"journal":{"name":"Journal de mycologie medicale","volume":"36 1","pages":"Article 101601"},"PeriodicalIF":1.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and diagnostic misperception of tuberculosis and systemic fungal infections","authors":"Karthikeyan Sundaram ,&nbsp;Sridhar Rathinam ,&nbsp;Venkataraman Prabhu","doi":"10.1016/j.mycmed.2026.101607","DOIUrl":"10.1016/j.mycmed.2026.101607","url":null,"abstract":"<div><div>Tuberculosis and systemic fungal diseases are opportunistic and challenging to diagnose. However, in immunocompromised people, especially people living with human immunodeficiency virus (PLHIV), the signs and symptoms of both diseases highly imitate each other. Primarily, chronic pulmonary aspergillosis (CPA) could have similar clinical characteristics to tuberculosis in lungs, and it is a major diagnostic challenge. Thus, the aim of the review is to analyze the prevalence, clinical manifestation, and challenges associated with the diagnostic consequences of TB and fungal infections. Although pulmonary tuberculosis (PTB) is routinely ruled out before a chronic pulmonary aspergillosis diagnosis and is widely accepted as an alternate diagnosis of CPA, the contrary is infrequent. Patients with chronic pulmonary aspergillosis usually exhibit a Th2 cytokine profile and may produce little or no IFN-γ. When fibrosis and cavitation appear on chest imaging in CPA, these patients may be misdiagnosed and neglected, which could have detrimental effects. Aspergillus-specific IgG serology is crucial for differentiating PTB and PTB relapse from CPA. Likewise, other fungal infections such as mucormycosis, cryptococcosis, histoplasmosis, and blastomycosis also reveal similar clinical manifestations to tuberculosis. Thereby, radiographic analysis is a typical diagnostic method; however, it cannot reliably detect illness symptoms. Consequently. GeneXpert can detect TB and resistance of RIF/INH in the short period, while CT imaging is better for chronic pulmonary aspergillosis and other fungal infections.</div></div>","PeriodicalId":14824,"journal":{"name":"Journal de mycologie medicale","volume":"36 1","pages":"Article 101607"},"PeriodicalIF":1.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “In vitro Susceptibilities to caspofungin of Candida spp. isolated from the Polyvalent Intensive Care Unit of Fattouma Bourguiba University Hospital: First report of resistant mutants in Tunisia” [J Mycol Med (2026) 101601]","authors":"Sameh Belgacem ,&nbsp;Wissal Chebil ,&nbsp;Ichrak Ferjani ,&nbsp;Donia Ghedira ,&nbsp;Maha Mastouri ,&nbsp;Hamouda Babba","doi":"10.1016/j.mycmed.2026.101606","DOIUrl":"10.1016/j.mycmed.2026.101606","url":null,"abstract":"","PeriodicalId":14824,"journal":{"name":"Journal de mycologie medicale","volume":"36 1","pages":"Article 101606"},"PeriodicalIF":1.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vulvo-vaginal candidiasis at the Zion Clinical Laboratory (Yaounde-Cameroon): risk factors, species distribution and antifungal susceptibility testing","authors":"Thierry Kammalac Ngouana ,&nbsp;Aude Ngueguim Dougue ,&nbsp;Vincent Ngouana ,&nbsp;Romeo Fouemene Tsayem ,&nbsp;Youssouf Hamdan Mahamat ,&nbsp;Fabrice Fekam Boyom F ,&nbsp;Stephane Ranque","doi":"10.1016/j.mycmed.2025.101590","DOIUrl":"10.1016/j.mycmed.2025.101590","url":null,"abstract":"<div><div>Background: Vulvovaginal candidiasis (VVC) is a common infection affecting women of reproductive age, associated with various risk factors. Advances in diagnosis and treatment are ongoing, but antifungal resistance remains a concern. This study aimed to evaluate risk factors, species distribution, and antifungal susceptibility of yeast isolates from reproductive-age women at Zion Clinical Laboratory, Yaoundé, Cameroon.</div><div>Materials and Methods: A total of 305 women suspected of vaginitis were enrolled. Socio-demographic and risk factor data were collected. Vaginal swabs were cultured on Sabouraud dextrose agar and CHROMagar <em>Candida</em>. Species identification was performed using MALDI-TOF mass spectrometry. Antifungal susceptibility testing was conducted with the Sensititre Yeast One kit to determine minimal inhibitory concentrations (MICs) for multiple antifungals.</div><div>Results: The prevalence of VVC was 32.1 %, significantly associated with age (women aged 21 to 36 years showing higher susceptibility to VVC; <em>P</em> = 0.0001) and vaginal douching (<em>P</em> = 0.0004). Eleven yeast species were identified, with <em>Candida albicans</em> predominating (64.2 %), followed by <em>C. orthopsilosis</em> (15.1 %), <em>Nakaseomyces glabratus</em> (<em>C. glabrata</em>) (4.7 %), and <em>C. tropicalis</em> (3.8 %). Most isolates were highly susceptible (&gt;90 %) to amphotericin B but showed reduced susceptibility to azoles, particularly fluconazole (Diflucan).</div><div>Conclusion: VVC affects nearly one-third of symptomatic reproductive-age women in this setting, with age and vaginal douching as significant risk factors. The predominance of <em>C. albicans</em> alongside diverse non-<em>albicans</em> species highlights the need for species-level identification. Reduced azole susceptibility stresses the importance of antifungal susceptibility testing to guide effective treatment and prevent resistance. Education on modifiable risk factors is also essential to reduce VVC incidence.</div></div>","PeriodicalId":14824,"journal":{"name":"Journal de mycologie medicale","volume":"36 1","pages":"Article 101590"},"PeriodicalIF":1.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjunctive hyperbaric oxygen combined with surgery and antifungal therapy for the management of soft tissue mucormycosis: a case report and review of the literature","authors":"Pauline Kapustin ,&nbsp;Aline Munting ,&nbsp;Benoît Desgraz ,&nbsp;Etienne Menager ,&nbsp;Jérémy Brühlmann ,&nbsp;Jocelyn Corbaz ,&nbsp;Truong-Thanh Pham ,&nbsp;Sylvain Meylan ,&nbsp;Daniel Wagner ,&nbsp;Yves Harder ,&nbsp;Frederic Lamoth","doi":"10.1016/j.mycmed.2026.101610","DOIUrl":"10.1016/j.mycmed.2026.101610","url":null,"abstract":"<div><div>Soft tissue mucormycosis is a rare fungal infection that can develop on contaminated wounds. We report a case of <em>Mucor circinelloides</em> ankle infection in an immunocompetent man following a high-energy motorcycle accident, which has successfully been treated by surgery (multiple debridements, arthrodesis, soft tissue defect reconstruction with flap and skin graft), systemic antifungal therapy (initial liposomal amphotericin B followed by isavuconazole) and hyperbaric oxygen. This case highlights the therapeutic challenges and need for a multidisciplinary approach of such infection.</div></div>","PeriodicalId":14824,"journal":{"name":"Journal de mycologie medicale","volume":"36 1","pages":"Article 101610"},"PeriodicalIF":1.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel antifungal activity of broxyquinoline against ITC-Resistant mutants via inhibition of methionine aminopeptidase in Aspergillus fumigatus","authors":"Peiying Chen ,&nbsp;Siyuan Tao ,&nbsp;Simin Xu ,&nbsp;Yangyang Yong ,&nbsp;Fei Gao ,&nbsp;Yuan Chen ,&nbsp;Chujie Lu ,&nbsp;Wei Lin","doi":"10.1016/j.mycmed.2025.101577","DOIUrl":"10.1016/j.mycmed.2025.101577","url":null,"abstract":"<div><h3>Background</h3><div>A rising public health threat of invasive aspergillosis causing by azole-resistant <em>Aspergillus</em> species necessitates the development of novel antifungal agents. We performed a screening of antifungal compounds against azole-resistant fungi and broxyquinoline was identified. Our aim was to investigate its antifungal activities and antifungal mechanism.</div></div><div><h3>Methods</h3><div>Fungal susceptibility testing for broxyquinoline carried out by the broth-based microdilution methods. Cell viability treated by broxyquinoline was tested by resazurin dye testing. The synergistic effect of broxyquinoline and itraconazole was evaluated using checkboard assay. Enzyme activity was investigated with spectrophotometric methods. The key amino acid residues in the binding of broxyquinoline with <em>A. fumigatus</em> methionine aminopeptidase (<em>Af</em>MetAP) were indicated by structural analyses, site-directed mutagenesis, and microscale thermophoresis (MST) assays.</div></div><div><h3>Results</h3><div>Broxyquinoline has fungicidal activity against azole-resistant <em>A. fumigatus</em> and synergistic effects with itraconazole. Moreover, we discovered that broxyquinoline is strong inhibitor of <em>Af</em>MetAP through interacting with key residues T279A/W280A of <em>Af</em>MetAP1 and Y527A of <em>Af</em>MetAP2, and <em>in vivo,</em> the strains with high expression of <em>Af</em>MetAP are resistant to BQ.</div></div><div><h3>Conclusions</h3><div>Broxyquinoline has antifungal activities against azole-resistant <em>Aspergillus</em> spp. and is also a potentiator of ITC <em>in vitro. Af</em>MetAP may biologically targets to BQ <em>in vivo</em> regulating antifungal activity. T279A/W280A of <em>Af</em>MetAP1 and Y527A of <em>Af</em>MetAP2 are key amino acid sites to maintain stable interactions between broxyquinoline and target enzymes <em>Af</em>MetAP.</div></div>","PeriodicalId":14824,"journal":{"name":"Journal de mycologie medicale","volume":"35 4","pages":"Article 101577"},"PeriodicalIF":1.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145060681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}