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念珠菌血流分离株的抗真菌药敏谱及唑类耐药的分子机制

Antifungal drug susceptibility profiles and molecular mechanisms of azole resistance in Candida blood stream isolates.

作者信息

Yenişehirli Gülgün, Alıcı Ayşe, Yenişehirli Aydan

机构信息

Tokat Gaziosmanpaşa University, Faculty of Medicine, Department of Medical Microbiology, 60100, Tokat, Turkey.

Tatvan State Hospital, Medical Microbiology Laboratory, Bitlis, Turkey.

出版信息

Indian J Med Microbiol. 2023 Sep-Oct;45:100389. doi: 10.1016/j.ijmmb.2023.100389. Epub 2023 Jun 9.

DOI:10.1016/j.ijmmb.2023.100389
PMID:37573042
Abstract

PURPOSE

The purpose of this study was to determine the activity of fluconazole, voriconazole, posaconazole, amphotericin B, micafungin and caspofungin against Candida blood stream isolates and to investigate the molecular mechanisms of azole resistance in fluconazole resistant isolates.

METHODS

The in vitro susceptibilities of Candida isolates to fluconazole, voriconazole, posaconazole, amphotericin B, micafungin and caspofungin were tested by E-test ERG11, CDR1, CDR2 and MDR1 genes expression of fluconazole resistant, fluconazole (S-DD) and fluconazole intermediate resistant isolates were investigated by quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR).

RESULTS

C. albicans (41%) was the most frequently isolated fungal species from blood stream infections followed by C. parapsilosis (22%). All C. albicans isolates except one and all C. tropicalis isolates were found to be susceptible to fluconazole. Overall, 21% of C. glabrata isolates were resistant to fluconazole. None of the Candida isolates were found to be resistant to caspofungin except 2 ​C. glabrata isolates. Overexpression of ERG11 and CDR1 genes were detected in all fluconazole S-DD and fluconazole resistant C. glabrata isolates, while CDR2 overexpression was observed in 91% fluconazole S-DD and 67 of % fluconazole resistant C.glabrata isolates. The overexpression of MDR1, ERG11 and CDR1 genes were found 100%, 80% and 80%, respectively, in fluconazole resistant C. parapsilosis isolates.

CONCLUSION

Most of the Candida isolates were susceptible to posaconazole and caspofungin. Our data also highlighted that overexpression of efflux pump genes major cause of azole resistance.

摘要

目的

本研究旨在确定氟康唑、伏立康唑、泊沙康唑、两性霉素B、米卡芬净和卡泊芬净对念珠菌血流分离株的活性,并研究氟康唑耐药分离株中唑类耐药的分子机制。

方法

采用E-test法检测念珠菌分离株对氟康唑、伏立康唑、泊沙康唑、两性霉素B、米卡芬净和卡泊芬净的体外敏感性,通过定量实时逆转录聚合酶链反应(qRT-PCR)研究氟康唑耐药、氟康唑(敏感-剂量依赖型)和氟康唑中介耐药分离株的ERG11、CDR1、CDR2和MDR1基因表达。

结果

白色念珠菌(41%)是血流感染中最常分离出的真菌物种,其次是近平滑念珠菌(22%)。除1株外,所有白色念珠菌分离株和所有热带念珠菌分离株均对氟康唑敏感。总体而言,21%的光滑念珠菌分离株对氟康唑耐药。除2株光滑念珠菌分离株外,未发现念珠菌分离株对卡泊芬净耐药。在所有氟康唑敏感-剂量依赖型和氟康唑耐药的光滑念珠菌分离株中均检测到ERG11和CDR1基因的过表达,而在91%的氟康唑敏感-剂量依赖型和67%的氟康唑耐药光滑念珠菌分离株中观察到CDR2过表达。在氟康唑耐药的近平滑念珠菌分离株中,MDR1、ERG11和CDR1基因的过表达分别为100%、80%和80%。

结论

大多数念珠菌分离株对泊沙康唑和卡泊芬净敏感。我们的数据还突出表明,外排泵基因的过表达是唑类耐药的主要原因。

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