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Molecular characterization of Echinocandin resistance and the CHS3-mediated adaptive response in Candida glabrata bloodstream infections in Eastern China

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Publicado en:BMC Microbiology vol. 25 (2025), p. 1-12
Autor principal: Cong, Peishan
Otros Autores: Wang, Biao, He, Hong, Li, Xiaoying, Peng, Lijing, Liu, Ji, Guo, Hui, Sun, Guirong
Publicado:
Springer Nature B.V.
Materias:
United States > US
China
Infections
Transcriptomes
Software
Diabetes
Fungicides
Ventilators
Sequence analysis
Epidemiology
Mutation
Micafungin
Voriconazole
Drugs
Genomes
Nucleotide sequence
Antifungal agents
Genes
Candidemia
Patients
Health care facilities
Blood diseases
Itraconazole
Gene sequencing
Fluconazole
Antibiotics
DNA polymerase
Homologous recombination
Chitin
Functional analysis
Posaconazole
Genomic analysis
Echinocandins
Multilocus sequence typing
Social
Candida glabrata
Acceso en línea:Citation/Abstract
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Resumen:BackgroundCandidemia caused by Candida glabrata is a serious fungal infection, and rising echinocandin resistance presents a significant clinical challenge. Understanding the drug susceptibility profiles, molecular epidemiology, and mechanisms underlying adaptive echinocandin resistance in C. glabrata is crucial.ResultsA total of 106 C. glabrata strains were isolated from blood cultures of 103 candidemia patients across three medical centers in eastern China. Transcriptome sequencing and whole-genome sequence analysis were used to explore the genomic characteristics of echinocandin-resistant strains. Multi-locus sequence typing (MLST) categorized the isolates into 11 sequence types (STs), with ST7 being the most prevalent (67.9%). Drug susceptibility testing revealed a fluconazole resistance rate of 21.7%, while non-wild-type rates for voriconazole, itraconazole, and posaconazole were 23.6%, 7.5%, and 6.6%, respectively. One isolate (Q2-2) was resistant to all three echinocandins. Two isolates were resistant to micafungin and anidulafungin, respectively. Compared to the echinocandin-sensitive strains, the expression of the Chitin synthetase 3 (CHS3) gene was significantly upregulated in echinocandin-resistant strains. Functional analysis of a CHS3-overexpressing strain (ATCC2001-CHS3-OE), generated through homologous recombination, confirmed echinocandin resistance. Conversely, a CHS3 knockout strain (Q2-2-CHS3Δ) exhibited susceptibility to echinocandins.ConclusionsOur findings suggest that CHS3 plays a critical compensatory role in echinocandin resistance in C. glabrata, offering a promising target for developing future antifungal strategies.
ISSN:1471-2180
DOI:10.1186/s12866-025-04155-5
Fuente:Health & Medical Collection