Recently, azole-resistant Aspergillus fumigatus containing a 34-bp or 46-bp tandem repeat in the promoter region of cyp51A combined with amino acid substitution(s) has appeared in the environment worldwide, including several Asian countries. In this study, we isolated the 34-bp tandem repeat-containing azole-resistant A. fumigatus strain OKH50 from a patient in Japan in May 2016. The patient had not been treated with medical azoles before the strain isolation, suggesting that the resistant property was acquired before infection. In addition, the patient had not traveled overseas. Our analysis of short tandem repeats of the strain indicates that the strain is strongly related to the 34-bp tandem repeat-containing isolates from European countries and Asia-Oceania countries but not to susceptible isolates from Japan, suggesting that the strain was introduced from overseas and might spread in Japan.
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http://dx.doi.org/10.1016/j.jiac.2016.12.004 | DOI Listing |
J Fungi (Basel)
November 2024
Sir John Walsh Research Institute, Faculty of Dentistry, University of Otago, Dunedin 9016, New Zealand.
is intrinsically resistant to the widely used antifungal fluconazole, and therapeutic failure can result from acquired resistance to voriconazole, the primary treatment for invasive aspergillosis. The molecular basis of substrate specificity and innate and acquired resistance of to azole drugs were addressed using crystal structures, molecular models, and expression in of the sterol 14α-demethylase isoforms AfCYP51A and AfCYP51B targeted by azole drugs, together with their cognate reductase AfCPRA2 and AfERG6 (sterol 24-C-methyltransferase). As predicted by molecular modelling, functional expression of CYP51A and B required eburicol and not lanosterol.
View Article and Find Full Text PDFNat Commun
December 2024
Manchester Fungal Infection Group, Division of Evolution, Infection, and Genomics, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
The environmental use of azole fungicides has led to selective sweeps across multiple loci in the Aspergillus fumigatus genome causing the rapid global expansion of a genetically distinct cluster of resistant genotypes. Isolates within this cluster are also more likely to be resistant to agricultural antifungals with unrelated modes of action. Here we show that this cluster is not only multi-azole resistant but has increased propensity to develop resistance to next generation antifungals because of variants in the DNA mismatch repair system.
View Article and Find Full Text PDFSci Total Environ
January 2025
Dept. Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.
Emergence of azole-resistant Aspergillus fumigatus represents a concern for public health worldwide. Here we applied a spatial analysis to a large number of records on A. fumigatus azole resistance in the Netherlands to evaluate the relationship of a set of environmental factors with the emergence of resistant isolates and to identify the potential risk areas.
View Article and Find Full Text PDFInt J Pharm
December 2024
School of Pharmacy and Pharmaceutical Science, Trinity College Dublin, Dublin, Ireland; SSPC, The Science Foundation Ireland Research Centre for Pharmaceuticals, Ireland. Electronic address:
Azole-resistant Aspergillus fumigatus (A. fumigatus) is an emerging worldwide pathogen. Pulmonary aspergillosis primarily affects severely immunocompromised patients and is also a particularly critical condition for cystic fibrosis (CF) patients.
View Article and Find Full Text PDFMed Mycol
November 2024
Laboratoire de Parasitologie-Mycologie, AP-HP, CHU Bichat-Claude Bernard, 75018 Paris, France.
We evaluated the combined performance of itraconazole and voriconazole Etest® gradient concentration strips for the detection of Aspergillus fumigatus azole resistance associated with cyp51a mutations confirmed by gene sequencing. Among 118 A. fumigatus clinical isolates collected in a French center, 6 (5%) had azole resistance mutations, 5 of which were probably of environmental origin.
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