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分析来自埃及亚历山大的临床热带假丝酵母菌分离株中 CDR1 和 MDR1 基因的表达和 ERG11 取代。

Analysis of CDR1 and MDR1 Gene Expression and ERG11 Substitutions in Clinical Candida tropicalis Isolates from Alexandria, Egypt.

机构信息

Department of Microbiology and Biotechnology, Division of Clinical and Biological Sciences, College of Pharmacy, Arab Academy for Science, Technology and Maritime Transport (AASTMT), Alexandria, Egypt.

Department of Microbiology, Medical Research Institute, Alexandria University, Alexandria, Egypt.

出版信息

Braz J Microbiol. 2023 Dec;54(4):2609-2615. doi: 10.1007/s42770-023-01106-y. Epub 2023 Aug 22.

DOI:10.1007/s42770-023-01106-y
PMID:37606863
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10689625/
Abstract

INTRODUCTION

Candida tropicalis is a common non-albicans Candida (NAC) species that causes numerous fungal infections. Increasing antifungal resistance to azoles in NAC is becoming a major health problem worldwide; however, in Egypt, almost no data is available regarding fluconazole resistance mechanisms in C. tropicalis. The current study aims to investigate two possible important molecular mechanisms involved in fluconazole resistance in C. tropicalis isolates.

MATERIALS

Fifty-four clinical C. tropicalis isolates were included. Identification and antifungal susceptibility profiles of the isolates were carried out using the VITEK 2 compact system. The molecular investigation of fluconazole resistance included the expression of the CDR1 and MDR1 genes by quantitative real-time RT-PCR as well as the sequence analysis of the ERG11 gene.

RESULTS

Antifungal susceptibility testing identified 30 fluconazole-non-susceptible isolates. Statistically, CDR1 gene expression in fluconazole-non-susceptible isolates was significantly higher than that in fluconazole-susceptible isolates, with MDR1 gene expression levels that were similar in both non-susceptible and susceptible isolates. Sequence analysis of the ERG11 gene of 26 fluconazole-resistant isolates identified two missense mutations: A395T (Y132F) and G1390A (G464S).

CONCLUSIONS

This study has highlighted the role of overexpression of the CDR1 gene and ERG11 gene mutations in fluconazole non-susceptibility. Further studies in Egypt are required to investigate other possible molecular mechanisms involved in azole resistance.

摘要

简介

热带假丝酵母菌是一种常见的非白假丝酵母菌(NAC),可引起多种真菌感染。NAC 对唑类药物的抗药性日益增加,成为全球范围内的一个主要健康问题;然而,在埃及,几乎没有关于热带假丝酵母菌对氟康唑耐药机制的数据。本研究旨在探讨两种可能涉及热带假丝酵母菌氟康唑耐药的重要分子机制。

材料

纳入了 54 株临床分离的热带假丝酵母菌。使用 VITEK 2 compact 系统进行鉴定和抗真菌药敏谱分析。氟康唑耐药的分子研究包括通过实时定量 RT-PCR 检测 CDR1 和 MDR1 基因的表达,以及 ERG11 基因的序列分析。

结果

抗真菌药敏试验鉴定出 30 株氟康唑非敏感性菌株。统计学分析显示,氟康唑非敏感性菌株中 CDR1 基因的表达显著高于氟康唑敏感性菌株,而 MDR1 基因的表达在非敏感性和敏感性菌株中相似。对 26 株氟康唑耐药株 ERG11 基因的序列分析发现了两种错义突变:A395T(Y132F)和 G1390A(G464S)。

结论

本研究强调了 CDR1 基因过度表达和 ERG11 基因突变在氟康唑非敏感性中的作用。需要在埃及进行进一步研究,以探讨唑类药物耐药性涉及的其他可能的分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ea/10689625/b8d8fb0229b6/42770_2023_1106_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ea/10689625/b8d8fb0229b6/42770_2023_1106_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ea/10689625/b8d8fb0229b6/42770_2023_1106_Fig1_HTML.jpg

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