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比较基因组学揭示了耐碳青霉烯类细菌中氟喹诺酮耐药决定因素及外膜孔蛋白F缺失情况。

Comparative Genomics Revealed Fluoroquinolone Resistance Determinants and OmpF Deletion in Carbapenem-Resistant .

作者信息

Yang Wan-Ting, Chiu I-Ju, Huang Yao-Ting, Liu Po-Yu

机构信息

Division of Infection, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.

Department of Computer Science and Information Engineering, National Chung Cheng University, Chia-Yi, Taiwan.

出版信息

Front Microbiol. 2022 Apr 18;13:886428. doi: 10.3389/fmicb.2022.886428. eCollection 2022.

Abstract

() is a major causative organism of complicated urinary tract infections, bloodstream infections, and pneumonia. With the widespread use of antimicrobial agents, the prevalence of carbapenem resistance in has been increasing with limited therapeutic options. Fluoroquinolone remains a choice in carbapenem-resistant that were once susceptible to the drug. Despite robust studies on the fluoroquinolone-resistant mechanisms of , few studies focused specifically on the group of CREc. In this study, we used comparative genomics to identify the fluoroquinolone-resistant mechanisms of CREc and detected gyrA D87N mutation in all the fluoroquinolone-resistant and . Moreover, to investigate the mechanism underlying non-carbapenemase-producing carbapenem-resistant , we targeted the complete genome sequences for in-depth analysis and found a deletion in OmpF (DEL264-269) that might contribute to carbapenem resistance, which has not been reported before. Further studies focusing on the impact of these mutations on the expression levels are warranted. We further investigate the MLST, serotype, fimH type, phylogroup, and clinical characteristics of the . Combination analysis of clinical and genomic characteristics suggests the polyclonal and highly diverse nature of the in Taiwan. This study provides an insight into the molecular epidemiology of CREc in Taiwan.

摘要

()是复杂性尿路感染、血流感染和肺炎的主要致病微生物。随着抗菌药物的广泛使用,()对碳青霉烯类耐药的发生率不断上升,治疗选择有限。氟喹诺酮类药物仍是对该药物曾经敏感的耐碳青霉烯类()的一种选择。尽管对()的氟喹诺酮类耐药机制进行了大量研究,但很少有研究专门针对耐碳青霉烯类大肠埃希菌(CREc)这一群体。在本研究中,我们使用比较基因组学来确定CREc的氟喹诺酮类耐药机制,并在所有耐氟喹诺酮类()中检测到gyrA D87N突变。此外,为了研究非产碳青霉烯酶的耐碳青霉烯类()的潜在机制,我们针对完整基因组序列进行深入分析,发现外膜孔蛋白F(OmpF)存在一个缺失(DEL264 - 269),这可能导致碳青霉烯类耐药,此前尚未见报道。有必要进一步开展研究关注这些突变对表达水平的影响。我们进一步研究了()的多位点序列分型(MLST)、血清型、菌毛蛋白H(fimH)类型、系统发育群和临床特征。临床和基因组特征的联合分析表明台湾地区()具有多克隆和高度多样性的特点。本研究为台湾地区CREc的分子流行病学提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c74e/9062692/f21e1bf43a6a/fmicb-13-886428-g0001.jpg

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