MycopathologiaPub Date : 2025-05-31DOI: 10.1007/s11046-025-00955-5
Ainoa Nieto-Claudín, Samara Zeas-Bermeo, Ma Paz Guillén-Liger, Sharon L Deem, Carlos Sacristán, Gislayne Mendoza-Alcívar, Rodrigo Caroca-Cáceres
{"title":"Fungi Matter: Aphanoascella galapagosensis Associated with Carapace Lesions in Free-Living Galapagos Tortoises.","authors":"Ainoa Nieto-Claudín, Samara Zeas-Bermeo, Ma Paz Guillén-Liger, Sharon L Deem, Carlos Sacristán, Gislayne Mendoza-Alcívar, Rodrigo Caroca-Cáceres","doi":"10.1007/s11046-025-00955-5","DOIUrl":"10.1007/s11046-025-00955-5","url":null,"abstract":"<p><p>Galapagos giant tortoises are among the most iconic reptile species on earth; however, an increase in anthropogenic activities has created new challenges for their health and well-being. The presence of whitish lesions on the carapace of Galapagos tortoises (Chelonoidis spp.) was previously described, potentially due to fungal growths, but its etiology remained unexplored. Aiming to close this gap, we analyzed carapace scrapes from six different species of free-living giant tortoises of Santa Cruz, Isabela, San Cristobal, and Española islands. In total, we tested 145 fresh and frozen carapace scrapes from 145 individuals with carapace whitish lesions (W-L, n = 80) and without them (W-O, n = 65), using panfungal endpoint PCRs for the ITS and D1-D2 regions. Aphanoascella galapagosensis was detected in W-L samples from all tortoise species and in none of the W-O samples. Four A. galapagosensis nucleotide sequence types (ST) obtained by using the D1-D2 protocol were identified in these tortoises; ST1 was detected on Santa Cruz, Isabela, and Española Islands whereas ST2 and ST3 were only detected on Isabela, and ST4 on San Cristobal. Neodevriesia spp. and Elsinoe spp. were the most common microorganisms found in W-O samples. These results suggest that A. galapagosensis is the etiological agent of whitish lesions in tortoise carapace contributing to baseline data on carapace fungi in giant Galapagos tortoises. Further research is needed to assess the prevalence and potential pathogenicity of A. galapagosensis and its impact for the conservation of these endangered species.</p>","PeriodicalId":19017,"journal":{"name":"Mycopathologia","volume":"190 3","pages":"48"},"PeriodicalIF":3.6,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MycopathologiaPub Date : 2025-05-30DOI: 10.1007/s11046-025-00956-4
Igor Massahiro de Souza Suguiura, Heinrik Makoto de Souza Suguiura, Lilian Cristiane Baeza, Eiko Nakagawa Itano, Mario Augusto Ono
{"title":"Antigenic Similarity Between Different Paracoccidioides Species in a Murine Model of Paracoccidioidomycosis Reveals High IgG Avidity for the 70 kDa Antigen.","authors":"Igor Massahiro de Souza Suguiura, Heinrik Makoto de Souza Suguiura, Lilian Cristiane Baeza, Eiko Nakagawa Itano, Mario Augusto Ono","doi":"10.1007/s11046-025-00956-4","DOIUrl":"10.1007/s11046-025-00956-4","url":null,"abstract":"<p><p>Since the new taxonomic proposal for differentiating Paracoccidioides species, many questions have emerged regarding its relevance beyond molecular analysis. Geographical distribution, pathogenesis, morphology, and virulence are still under debate to confirm the diverse genotypic profile of these species. In this study, we evaluated the serological differences of mice experimentally infected with Paracoccidioides brasiliensis sensu stricto, Paracoccidioides restrepiensis, Paracoccidioides americana, Paracoccidioides venezuelensis, and Paracoccidioides lutzii. The serological differences between the Paracoccidioides spp. were evaluated by ELISA, Western blot, and avidity Western blot using cell-free antigens (CFA) of the heterologous and homologous Paracoccidioides isolates used for the experimental infection. As expected, all Paracoccidioides spp. isolates shared several antigens that were recognized by mouse antibodies in both ELISA and Western blot. While ELISA results revealed differences in antigen recognition among isolates, these differences were not consistent at the species level. The number of bands identified in the immunoblotting varied among the isolates, with certain antigens, such as those from Pb01, a P. lutzii isolate, being less recognized across groups. We also observed overall differences in IgG avidity toward the CFA antigens. Notably, higher avidity was observed for the ~ 70 kDa antigen when compared to other antigens such as 79, 64, 54 and 43 kDa, the latter being gp43, the most studied and widely used glycoprotein for paracoccidioidomycosis immunodiagnosis.</p>","PeriodicalId":19017,"journal":{"name":"Mycopathologia","volume":"190 3","pages":"46"},"PeriodicalIF":3.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MycopathologiaPub Date : 2025-05-26DOI: 10.1007/s11046-025-00952-8
Ayman K El Essawy, Abdul Rahman Al Amri
{"title":"Emergent Aspergillus tamarii and Fusarium falciforme Keratitis.","authors":"Ayman K El Essawy, Abdul Rahman Al Amri","doi":"10.1007/s11046-025-00952-8","DOIUrl":"10.1007/s11046-025-00952-8","url":null,"abstract":"","PeriodicalId":19017,"journal":{"name":"Mycopathologia","volume":"190 3","pages":"45"},"PeriodicalIF":3.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MycopathologiaPub Date : 2025-05-18DOI: 10.1007/s11046-025-00949-3
Wanting Luo, Guoliang Wang, Hongyu Chang, Guiming Liu, He Zhu, Haitao Li
{"title":"Transcriptomics Uncovers Key Genes for Photodynamic Killing on Trichosporon asahii Biofilms.","authors":"Wanting Luo, Guoliang Wang, Hongyu Chang, Guiming Liu, He Zhu, Haitao Li","doi":"10.1007/s11046-025-00949-3","DOIUrl":"10.1007/s11046-025-00949-3","url":null,"abstract":"<p><strong>Background: </strong>The escalating threat of antifungal resistance stemming from Trichosporon asahii (T. asahii) biofilms necessitates the pursuit of innovative therapeutic strategies. Among these approaches, 5-aminolevulinic acid (ALA) photodynamic therapy (PDT), an emerging therapeutic modality, has exhibited promising potential in eradicating T. asahii biofilms.</p><p><strong>Methods: </strong>The inhibitory activity was evaluated by confocal laser scanning microscopy. To delve deeper into the efficacy of ALA-PDT in eliminating T. asahii biofilms, we conducted a comprehensive transcriptional analysis utilizing transcriptome sequencing.</p><p><strong>Results: </strong>ALA-PDT demonstrated a profound inhibitory effect on the viability of T. asahii biofilms. Our investigation unveiled 2720 differentially expressed genes following exposure to ALA-PDT. Subsequent meticulous scrutiny allowed for the annotation of genes with a ≥ twofold change in transcription, focusing on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. Particularly noteworthy were the upregulated genes associated with oxidation-reduction processes, oxidoreductase activity, and catalytic activity. Conversely, the downregulated genes were linked to ATP binding, protein phosphorylation, and protein kinase activity. Additionally, we observed a surge in the transcription of genes that may be involved in oxidative stress (e.g., A1Q1_05494) as well as genes that may be involved in morphogenesis and biofilm formation (e.g., A1Q1_04029, A1Q1_01345, A1Q1_08069, and A1Q1_01456) following ALA-PDT treatment.</p><p><strong>Conclusions: </strong>Our findings underscore the substantial impact of ALA-PDT on the transcriptional regulation of genes related to oxidative stress, morphogenesis, and biofilm formation, paving the way for novel therapeutic avenues in combating T. asahii biofilms.</p>","PeriodicalId":19017,"journal":{"name":"Mycopathologia","volume":"190 3","pages":"42"},"PeriodicalIF":3.6,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Synergistic Antifungal Activity of Pentamidine and Auranofin Against Multidrug-Resistant Candida auris.","authors":"Yasmim Isabel Retore, Fabíola Lucini, Simone Simionatto, Luana Rossato","doi":"10.1007/s11046-025-00948-4","DOIUrl":"10.1007/s11046-025-00948-4","url":null,"abstract":"<p><strong>Background: </strong>Candida auris is a significant clinical concern due to its ability to cause outbreaks in healthcare settings and its common resistance to current treatments. This highlights the need for alternative therapies. Drug repurposing offers a promising approach, and the combination of pentamidine (antiprotozoal) and auranofin (anti-rheumatic) has shown potential antifungal activity against Candida species, including C. auris. This study aimed to evaluate the antifungal activity of pentamidine and auranofin, both individually and in combination, against C. auris.</p><p><strong>Methods: </strong>Minimum Inhibitory Concentrations (MICs) were determined following CLSI guidelines, and drug interactions were assessed using the checkerboard microdilution method. Additional evaluations included growth inhibition, antibiofilm activity, cell damage, sorbitol protection, and efflux pump inhibition. Nucleotide leakage and cell membrane permeability were analyzed using biochemical assays. In vivo efficacy was tested using a Tenebrio molitor larvae model infected with C. auris.</p><p><strong>Results: </strong>The MICs of pentamidine against C. auris ranged from 16 to 128 μg/mL, showing fungicidal activity. The combination with auranofin had a synergistic effect (FICI: 0.37) and exhibited a fungistatic effect in growth inhibition assays. Auranofin was most effective at inhibiting biofilm formation. Pentamidine impaired mitochondrial function, leading to cellular respiration issues and membrane damage. Efflux pump assays indicated activation by both drugs, potentially influencing resistance. In vivo tests showed both drugs significantly improved survival rates in infected larvae compared to fluconazole.</p><p><strong>Conclusion: </strong>In conclusion, pentamidine and auranofin, either individually or in combination, are promising treatments for C. auris and warrant further research into optimal dosing and combination strategies.</p>","PeriodicalId":19017,"journal":{"name":"Mycopathologia","volume":"190 3","pages":"41"},"PeriodicalIF":3.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MycopathologiaPub Date : 2025-05-05DOI: 10.1007/s11046-025-00947-5
Jintong Wu, Zijie Tang, Su Wang, Yuxin Qiu, Xinyu Nie, Chengxin Li, Rui Wang
{"title":"Superficial Mycoses: A Mapping Through Bibliometric Research.","authors":"Jintong Wu, Zijie Tang, Su Wang, Yuxin Qiu, Xinyu Nie, Chengxin Li, Rui Wang","doi":"10.1007/s11046-025-00947-5","DOIUrl":"10.1007/s11046-025-00947-5","url":null,"abstract":"<p><p>Superficial mycosis is a common and recurrent infectious skin disease. It poses significant challenges, with high recurrence rates and drug resistance, which notably diminishes the quality of life for patients and presents substantial public health issues. Numerous publications on superficial mycosis have posed significant challenges for researchers to manage the overwhelming amount of information effectively. This study aims to comprehensively explore the current state and latest advancements in global research through bibliometric techniques, providing a holistic appraisal of the field. Publications from the Web of Science Core Collection database were analyzed, including publications and citations, author groups and their countries and regions, journal categories, publishing institutions, and keywords using Excel 2019, VOSviewer, and CiteSpace. A total of 2206 papers were reviewed, showing a stable increase in research output from 2020 to 2022 and a predicted growth trend. The United States and India published the most significant number of research papers. Key research areas identified were \"Outbreak\", \"Desorption ionization time\", \"Formulations\", \"Impact\", \"Dermatophyte\", and \"Dermoscopy\". This bibliometric analysis provides a comprehensive visualized map to describe current and development trends. Advanced diagnostic technologies and innovative delivery systems are key current research priorities and will remain focal areas in this field.</p>","PeriodicalId":19017,"journal":{"name":"Mycopathologia","volume":"190 3","pages":"39"},"PeriodicalIF":3.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Deciphering Fluconazole Resistance in Candida auris clade V: The Role of Efflux Pump Gene Expression and Ergosterol Pathway Mutations.","authors":"Robab Ebrahimi Barough, Mahdi Abastabar, Maryam Moazeni, Javad Javidnia, Reza Valadan, Azadeh Bandegani, Mohsen Nosratabadi, Iman Haghani, Bram Spruijtenburg, Darius Armstrong-James, Hamid Badali","doi":"10.1007/s11046-025-00945-7","DOIUrl":"10.1007/s11046-025-00945-7","url":null,"abstract":"<p><p>Candida auris is an emerging multidrug-resistant yeast pathogen that poses a serious global health threat. In particular, fluconazole resistance is common in C. auris, posing challenges for treating invasive infections. Understanding the genetic and molecular mechanisms underlying fluconazole resistance in C. auris is crucial for developing effective control strategies. The current study investigated the genetic and molecular basis of fluconazole resistance in C. auris clade V isolates. Furthermore, we examined mutations in ergosterol biosynthesis genes and expression of efflux pump genes in fluconazole-resistant versus susceptible in strains Clade V. Two C. auris isolates, one fluconazole-resistant, and one fluconazole-susceptible, were subjected to qPCR analysis of efflux pump gene (CDR1, CDR2, MDR1, MDR2) expression. Protein structure modeling was also performed to assess the impact of mutation in the ergosterol biosynthesis gene (ERG11) on antifungal drug accessibility. qPCR analysis revealed no significant difference in the expression levels of the efflux pump genes CDR1, CDR2, and MDR1 between the resistant and susceptible strains. Protein structure modeling indicated that the Y132F mutation in ERG11 likely altered fluconazole binding and accessibility. This study provides insights into the genetic and molecular mechanisms underpinning fluconazole resistance in C. auris Clade V. The findings highlight the critical roles of ERG11 mutation in mediating azole resistance in this emerging fungal pathogen.</p>","PeriodicalId":19017,"journal":{"name":"Mycopathologia","volume":"190 3","pages":"38"},"PeriodicalIF":3.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MycopathologiaPub Date : 2025-04-15DOI: 10.1007/s11046-025-00944-8
Koos Korsten, Bert Gerrits van den Ende, Rick D Pique, Ferry Hagen, Karin van Dijk
{"title":"Keep the Hospital Clean: Diagnostic Performance of Ten Different Molecular and Culture-Based Methods to Detect Candidozyma (Candida) auris.","authors":"Koos Korsten, Bert Gerrits van den Ende, Rick D Pique, Ferry Hagen, Karin van Dijk","doi":"10.1007/s11046-025-00944-8","DOIUrl":"10.1007/s11046-025-00944-8","url":null,"abstract":"<p><strong>Rationale: </strong>Candidozyma auris (formerly Candida auris) is a globally emerging potentially multi-drug resistant human pathogenic yeast. To detect C. auris we aimed to compare different culture-, and molecular-based methods.</p><p><strong>Methods: </strong>Rectal swabs routinely collected in clinical care were spiked with different concentrations of C. auris. Co-infection/colonization was mimicked by spiking part of these samples with other pathogenic Candida species. Spiked materials were cultured at 37 or 42 °C using CHROMagar Candida and CHROMagar Candida Plus plates. In parallel, samples were incubated in a dulcitol salt enrichment broth. Additionally, we compared seven in-house and commercial molecular tests on the direct material and from the broth one day after inoculation.</p><p><strong>Results: </strong>Culture-based methods showed sensitivities up to 100% within 48 h of incubation, although sensitivity decreased as low as 44% at lower concentrations (≤ 50 CFU per inoculum), in the presence of an abundance of other species and at higher temperature (42 °C). Incubation at 42 °C made visual identification possible since other species with similar colony morphologies did not grow at this temperature. No added value of using the dulcitol salt enrichment broth was found. qPCR on direct materials was highly sensitive and specific (both up to 100%) but major differences between various molecular tests were observed.</p><p><strong>Conclusion: </strong>We showed that both culture-based and molecular methods are sensitive for diagnosing C. auris. The clinical setting (routine screening versus an outbreak), local prevalence and the load in those that carry or are infected by C. auris are important factors to consider when determining which diagnostic tests should be employed.</p>","PeriodicalId":19017,"journal":{"name":"Mycopathologia","volume":"190 3","pages":"37"},"PeriodicalIF":3.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12000201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MycopathologiaPub Date : 2025-04-11DOI: 10.1007/s11046-025-00940-y
Xingye Meng, Xiao Liu, Li Li, Dongyan Zheng, Lingbing Zeng, Yanling Liu, Ruoyu Li, Min Zhu, Cunwei Cao, Xianwei Cao, Yinggai Song, Jin Yu
{"title":"Clinical Features of Invasive Fungal Disease in China Tertiary Hospital: A Prospective, Multicenter Study.","authors":"Xingye Meng, Xiao Liu, Li Li, Dongyan Zheng, Lingbing Zeng, Yanling Liu, Ruoyu Li, Min Zhu, Cunwei Cao, Xianwei Cao, Yinggai Song, Jin Yu","doi":"10.1007/s11046-025-00940-y","DOIUrl":"10.1007/s11046-025-00940-y","url":null,"abstract":"<p><p>Invasive fungal disease (IFD) has high morbidity and mortality, the spectrum of pathogenic fungi and high-risk groups have also changed. Fewer literature focus on the overall incidence of IFD in various departments of general hospitals. Among the adult inpatients in four Chinese tertiary hospitals located in Beijing, Shanghai, Nanning and Nanchang, proven or probable cases of IFD were included prospectively in this study between May 1, 2021 and May 1, 2022. The clinical data were collected and analyzed. A total of 330 patients (342 episodes) with 278 of proven and 64 of probable IFDs were included, including invasive candidiasis (IC) (132, 40.0%), cryptococcosis (64, 19.4%), invasive aspergillosis (IA) (54, 16.4%), Talaromyces marneffei (TsM) infection (43, 13.0%), Pneumocystis pneumonia (PCP) (16, 4.8%), mixed fungal infection (10, 3.0%), other mold or yeast infection. 37.9% occurred in elderly patients (age ≥ 65 years). Nosocomial infection accounted for 44.5%, the proportion of nosocomial infection was highest in patients with IC (81.8%). Diabetes (19.7%) was the most common underlying disease. 83.9% of the 342 episodes of IFD had evidence of fungal culture, while the proportion of microscopic examination and histopathology as mycological evidence was 26.9% and 3.5%, respectively. The cumulative all-cause mortality at 180 days after diagnosis of IFD was 38.5%. Age ≥ 65 years old (HR = 1.670, P = 0.009), ICU (HR = 2.002, P = 0.001), nosocomial infection (HR = 1.630, P = 0.016) and diabetes (HR = 1.679, P = 0.013) were associated with increased death in IFD patients. The prognosis of IFD patients was poor. Doctors should pay attention to nosocomial fungal infection especially in old and diabetes.</p>","PeriodicalId":19017,"journal":{"name":"Mycopathologia","volume":"190 3","pages":"36"},"PeriodicalIF":3.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Trends of Azole-Resistant Aspergillus Fumigatus Susceptibility Over 12 Years from a German ECMM Excellence Center.","authors":"Hedda Luise Verhasselt, Lara Thissen, Ulrike Scharmann, Silke Dittmer, Peter-Michael Rath, Joerg Steinmann, Lisa Kirchhoff","doi":"10.1007/s11046-025-00941-x","DOIUrl":"10.1007/s11046-025-00941-x","url":null,"abstract":"<p><p>Numbers of infections with azole-resistant Aspergillus fumigatus (ARAf) were rising in the last decades. We assessed ARAf susceptibility trends towards five antifungal agents (amphotericin B (AMB), itraconazole (ITR), voriconazole (VCZ), olorofim (OLO) and manogepix (MGX)) over twelve years in a German Excellence Center for Medical Mycology (ECMM). In addition, underlying mutations were studied and correlated with trends in minimum inhibitory concentration (MIC). Broth microdilution (BMD) was performed following EUCAST guidelines for 143 clinical ARAf isolates collected between the years 2011 and 2022 in a West German tertiary care centre. BMD was carried out for all antifungal agents in the following concentration ranges: 0.016-8 mg/L for AMB, ITR and VCZ as well as 0.001-0.5 mg/L for OLO and 0.004-2 mg/L for MGX. Molecular assays on mutations associated with antifungal resistance were performed for all 143 isolates (AsperGenius® 1.0, Pathonostics, Maastricht, The Netherlands) and for a total of ten non TR<sub>34</sub>/L98H and TR<sub>46</sub>/Y121F/T289A mutated ARAf isolates additional cyp51A sequencing was carried out. For all isolates, microdilution revealed a MIC<sub>50</sub> of > 8 mg/L for ITR, 4 mg/L for VCZ, 0.03 mg/L for OLO, 0.016 mg/L for MGX, and 0.5 mg/L for AMB. Considering EUCAST breakpoints, 97.9% of the strains (n = 140) were resistant to VCZ, 1.4% (n = 2) towards AMB and 92.3% towards ITR (n = 132). Molecular assays revealed 123 (86%) isolates with the azole resistance underlying mutation TR<sub>34</sub>/L98H, 10 (7%) with a TR<sub>46</sub>/Y121F/T289A mutation and 10 (7%) with other cyp51A mutations. A comparison of triazole MICs of isolates collected from 2011 to 2019 with the MICs of isolates collected between 2020 and 2022 revealed no significant differences for itraconazole (p = 0.543) and for voriconazole (p = 0.148),with a trend of increased geometric mean for ITR and VCZ MICs over time. MICs for OLO and MGX did not significantly differ between isolates with the distinct azole-resistance underlying mutations. Before 2016, the azole resistance underlying mutations were mainly TR<sub>34</sub>/L98H, but the portion of isolates with TR<sub>46</sub>/Y121F/T289A and other Cyp51A mutated isolates increased afterwards. We showed almost stable MICs for ITR and VCZ over twelve years in ARAf isolates from West Germany while occurring azole resistance underlying mutations varied with an increase in the proportion of TR<sub>46</sub>/Y121F/T289A and other Cyp51A mutations after 2016.</p>","PeriodicalId":19017,"journal":{"name":"Mycopathologia","volume":"190 2","pages":"34"},"PeriodicalIF":3.6,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}