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

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Vydáno v:BMC Microbiology vol. 25 (2025), p. 1-12
Hlavní autor: Cong, Peishan
Další autoři: Wang, Biao, He, Hong, Li, Xiaoying, Peng, Lijing, Liu, Ji, Guo, Hui, Sun, Guirong
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Springer Nature B.V.
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LEADER 00000nab a2200000uu 4500
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022 |a 1471-2180 
024 7 |a 10.1186/s12866-025-04155-5  |2 doi 
035 |a 3247129302 
045 2 |b d20250101  |b d20251231 
084 |a 58455  |2 nlm 
100 1 |a Cong, Peishan 
245 1 |a Molecular characterization of Echinocandin resistance and the <i>CHS3</i>-mediated adaptive response in <i>Candida glabrata</i> bloodstream infections in Eastern China 
260 |b Springer Nature B.V.  |c 2025 
513 |a Journal Article 
520 3 |a 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. 
651 4 |a United States--US 
651 4 |a China 
653 |a Infections 
653 |a Transcriptomes 
653 |a Software 
653 |a Diabetes 
653 |a Fungicides 
653 |a Ventilators 
653 |a Sequence analysis 
653 |a Epidemiology 
653 |a Mutation 
653 |a Micafungin 
653 |a Voriconazole 
653 |a Drugs 
653 |a Genomes 
653 |a Nucleotide sequence 
653 |a Antifungal agents 
653 |a Genes 
653 |a Candidemia 
653 |a Patients 
653 |a Health care facilities 
653 |a Blood diseases 
653 |a Itraconazole 
653 |a Gene sequencing 
653 |a Fluconazole 
653 |a Antibiotics 
653 |a DNA polymerase 
653 |a Homologous recombination 
653 |a Chitin 
653 |a Functional analysis 
653 |a Posaconazole 
653 |a Genomic analysis 
653 |a Echinocandins 
653 |a Multilocus sequence typing 
653 |a Social 
653 |a Candida glabrata 
700 1 |a Wang, Biao 
700 1 |a He, Hong 
700 1 |a Li, Xiaoying 
700 1 |a Peng, Lijing 
700 1 |a Liu, Ji 
700 1 |a Guo, Hui 
700 1 |a Sun, Guirong 
773 0 |t BMC Microbiology  |g vol. 25 (2025), p. 1-12 
786 0 |d ProQuest  |t Health & Medical Collection 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/3247129302/abstract/embedded/75I98GEZK8WCJMPQ?source=fedsrch 
856 4 0 |3 Full Text  |u https://www.proquest.com/docview/3247129302/fulltext/embedded/75I98GEZK8WCJMPQ?source=fedsrch 
856 4 0 |3 Full Text - PDF  |u https://www.proquest.com/docview/3247129302/fulltextPDF/embedded/75I98GEZK8WCJMPQ?source=fedsrch