Azole resistance in Candida glabrata clinical isolates from global surveillance is associated with efflux overexpression
Azole resistance in Candida glabrata clinical isolates from global surveillance is associated with efflux overexpression
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DOI：
10.1016/j.jgar.2022.05.004
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发表时间：
2022-06-03
影响因子：
4.6
通讯作者：
Pfaller, Michael A.
中科院分区：
文献类型：
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作者：
Castanheira, Mariana;Deshpande, Lalitagauri M.;Pfaller, Michael A.
目的：从一项全球调查中评估氟康唑耐药秃念珠菌的耐药机制和流行病学。方法：采用微量肉汤稀释参比法，对2018-2019年采集的2992株念珠菌进行药敏试验。采用qRT-PCR技术对氟康唑耐药的光秃菌分离株进行全基因组测序和基因表达分析。结果：561株CGLA菌株中，34株（6.1%）对氟康唑耐药。这些分离株来自11个国家，主要来自血液感染（79.4%）。所有对氟康唑耐药的秃僵菌分离株伏立康唑为非野生型，泊沙康唑为非野生型24/34株，伊曲康唑为非野生型2/34株。异唑康唑的MIC值为0.25 ~ 0.4 mg/L。耐氟康唑光秃菌分离株有14种不同的序列类型。所有分离株均未表现出氮唑靶蛋白ERG3或ERG11的变化。除2株氟康唑耐药菌株外，其余菌株均显示CgCDR1（22/34; 64.7%）和/或CgCDR2（26/34; 76.5%）过表达，16株菌株两种基因均过表达。未观察到CgSNQ2或ERG11过表达。在14株菌株中发现了转录因子CgPDR1的功能增益（GoF）改变。4个（11.8%）对一种或多种棘球白素不敏感的分离株有FKS2 HS1改变（2个S663P和2个F659Y/缺失）。结论：CgCDR1和/或CgCDR2的过表达驱动了氟康唑耐药的光斑田鼠。观察到PDR1中GoF的改变与毒性增加有关。需要药敏结果和监测数据来指导这些分离株的治疗。(c) 2022作者。由Elsevier Ltd代表国际抗微生物化疗学会发表。这是一篇基于CC BY-NC-ND许可的开放获取文章（http://creativecommons.org/licenses/by-nc-nd/4.0/）
Objectives: We evaluated the azole resistance mechanisms and epidemiology of fluconazole-resistant Candida glabrata from a global survey.Methods: A total of 2992 Candida spp. isolates collected during 2018-2019 were susceptibility tested by the broth microdilution reference method following CLSI guidelines. Fluconazole-resistant C. glabrata isolates were submitted to whole genome sequencing and gene expression assays using qRT-PCR.Results: Among 561 CGLA isolates tested, 34 (6.1%) were fluconazole resistant. These isolates were collected from 11 countries and mainly recovered from bloodstream infections (79.4%). All fluconazoleresistant C. glabrata isolates were non-wild type for voriconazole, 24/34 were non-wild type for posaconazole, but only 2/34 were non-wild type for itraconazole. Isavuconazole MIC values ranged from 0.25 to > 4 mg/L. Fluconazole-resistant C. glabrata isolates belonged to 14 different sequence types (ST). None of the isolates exhibited alterations in ERG3 or ERG11, the target of azoles. All but two fluconazoleresistant isolates displayed overexpression of CgCDR1 (22/34; 64.7%) and/or CgCDR2 (26/34; 76.5%), while 16 isolates had both genes overexpressed. Overexpression of CgSNQ2 or ERG11 was not observed. Gain of function (GoF) alterations in the transcription factor CgPDR1 were noted in 14 isolates. Four (11.8%) isolates that were nonsusceptible to one or more echinocandins had FKS2 HS1 alterations (2 S663P and 2 F659Y/deletion).Conclusion: Fluconazole-resistant C. glabrata was driven by overexpression of CgCDR1 and/or CgCDR2. GoF alterations in PDR1 that have been associated with increased virulence were observed. Susceptibility results and surveillance data are needed to guide treatment for these isolates.(c) 2022 The Authors. Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )