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纳米比亚阴道光滑念珠菌分离株的分子流行病学和抗菌药物耐药性研究。

Molecular epidemiology and antimicrobial resistance of vaginal Candida glabrata isolates in Namibia.

机构信息

Namibia University of Sciences and Technology, Department of Health and Applied Sciences, Windhoek 10005, Namibia.

University of Pretoria, Department of Medical Microbiology, Pretoria 0001, South Africa.

出版信息

Med Mycol. 2024 Jan 27;62(2). doi: 10.1093/mmy/myae009.

DOI:10.1093/mmy/myae009
PMID:38308518
Abstract

Candida glabrata is the most common non-albicans Candida species that causes vulvovaginal candidiasis (VVC). Given the intrinsically low susceptibility of C. glabrata to azole drugs, investigations into C. glabrata prevalence, fungal susceptibility profile, and molecular epidemiology are necessary to optimise the treatment of VVC. This molecular epidemiological study was conducted to determine antifungal drug profile, single nucleotide polymorphisms (SNPs) associated with phenotypic antifungal resistance and epidemic diversity of C. glabrata isolates from women with VVC in Namibia. Candida glabrata isolates were identified using phenotypic and molecular methods. Antifungal susceptibility of strains was determined for fluconazole, itraconazole, amphotericin B, and anidulafungin. Whole genome sequencing was used to determine SNPs in antifungal resistance genes and sequence type (ST) allocation. Among C. glabrata isolates, all (20/20; 100%) exhibited phenotypic resistance to the azole class antifungal drug, (fluconazole), and phenotypic susceptibility to the polyene class (amphotericin B), and the echinocandins (anidulafungin). Non-synonymous SNPs were identified in antifungal resistance genes of all fluconazole-resistant C. glabrata isolates including ERG6 (15%), ERG7 (15%), CgCDR1 (25%), CgPDR1 (60%), SNQ2 (10%), FKS1 (5.0%), FKS2 (5.0%), CgFPS1 (5.0%), and MSH2 (15%). ST15 (n = 8/20, 40%) was predominant. This study provides important insight into phenotypic and genotypic antifungal resistance across C. glabrata isolates from women with VVC in Namibia. In this study, azole resistance is determined by an extensive range of SNPs, while the observed polyene and echinocandin resistance-associated SNPs despite phenotypic susceptibility require further investigation.

摘要

光滑念珠菌是引起外阴阴道念珠菌病(VVC)的最常见非白念珠菌念珠菌。鉴于光滑念珠菌对唑类药物固有低敏感性,有必要对其流行率、真菌药敏谱和分子流行病学进行调查,以优化 VVC 的治疗。本分子流行病学研究旨在确定纳米比亚 VVC 女性中光滑念珠菌分离株的抗真菌药物谱、与表型抗真菌耐药性相关的单核苷酸多态性(SNP)和流行多样性。使用表型和分子方法鉴定光滑念珠菌分离株。对菌株的氟康唑、伊曲康唑、两性霉素 B 和安尼达弗林的药敏性进行了测定。全基因组测序用于确定抗真菌耐药基因和序列型(ST)分配的 SNP。在光滑念珠菌分离株中,所有(20/20;100%)对唑类抗真菌药物(氟康唑)表现出表型耐药,对多烯类(两性霉素 B)和棘白菌素类(安尼达弗林)表现出表型敏感性。所有氟康唑耐药的光滑念珠菌分离株的抗真菌耐药基因中均发现了非同义 SNP,包括 ERG6(15%)、ERG7(15%)、CgCDR1(25%)、CgPDR1(60%)、SNQ2(10%)、FKS1(5.0%)、FKS2(5.0%)、CgFPS1(5.0%)和 MSH2(15%)。ST15(n=8/20,40%)占优势。本研究为纳米比亚 VVC 女性中光滑念珠菌分离株的表型和基因型抗真菌耐药提供了重要见解。在本研究中,唑类耐药性由广泛的 SNP 决定,而观察到的多烯类和棘白菌素类耐药相关 SNP 尽管表型敏感,但仍需要进一步研究。

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