Genotypic, phenotypic, and in silico analysis of carbapenem-resistant Klebsiella pneumoniae

IF 1.5 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Indian journal of biochemistry & biophysics Pub Date : 2023-01-01 DOI:10.56042/ijbb.v60i9.3968

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引用次数: 0

Abstract

Due to an increase in serious infections and a lack of efficient therapies, Klebsiella pneumoniae has recently gained more recognition. The production of carbapenemases is one of the most common strategies by which K. pneumoniae acquire resistance to carbapenems which is considered the last resort of antibiotics. Previously collected isolates from different clinical settings and on the basis of their genetic profile, mainly the absence and presence of single or dual carbapenemases (OXA-181, OXA-232, NDM-1, NDM-5, NDM-5+OXA-181, and NDM-1+OXA-232), mutations in porins, and efflux pumps, seven isolates (M40, M52, M39, J20, M53, M49, and M17B) were selected. Its phenotypic resistance against two carbapenem drugs (ertapenem and meropenem) was checked and we found NDM-5 followed by OXA-181 and NDM-5+OXA-181 carrying isolates showed high MIC values. Further, no significant differences were observed either in the presence of efflux pumps or mutations in porins among isolates. By molecular docking, among single amino acid differences between OXA-181 and OXA-232 and with two amino acids differences between NDM-1 and NDM-5, OXA-232 and NDM-5 showed a higher binding affinity than OXA-181 and NDM-1 with both antibiotics. It is concluded that the presence of specific carbapenemases or combinations of the same can drastically increase MIC values. The presence of NDM-5, and OXA-181, or their combinations is more fatal than NDM-1+OXA-232.

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耐碳青霉烯肺炎克雷伯菌的基因型、表型和计算机分析

由于严重感染的增加和缺乏有效的治疗方法，肺炎克雷伯菌最近得到了更多的认识。碳青霉烯酶的产生是肺炎克雷伯菌获得碳青霉烯类耐药性的最常见策略之一，碳青霉烯类被认为是抗生素的最后手段。先前从不同临床环境收集的分离株，根据其遗传谱，主要是缺乏或存在单或双碳青霉烯酶(OXA-181, OXA-232, NDM-1, NDM-5, NDM-5+OXA-181和NDM-1+OXA-232)，孔蛋白突变和外排泵，选择7株(M40, M52, M39, J20, M53, M49和M17B)。对两种碳青霉烯类药物(埃他培南和美罗培南)的表型耐药进行了检测，发现NDM-5接OXA-181和NDM-5+OXA-181的分离株具有较高的MIC值。此外，在外排泵或孔蛋白突变的存在中，分离株之间没有观察到显着差异。通过分子对接，在OXA-181与OXA-232之间的单氨基酸差异以及NDM-1与NDM-5之间的两个氨基酸差异中，OXA-232和NDM-5与两种抗生素的结合亲和力均高于OXA-181和NDM-1。由此可见，特定碳青霉烯酶或其组合的存在可显著提高MIC值。NDM-5和OXA-181的存在或它们的组合比NDM-1+OXA-232更致命。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Indian journal of biochemistry & biophysics 生物-生化与分子生物学

CiteScore

2.90

自引率

50.00%

发文量

审稿时长

3 months

期刊介绍： Started in 1964, this journal publishes original research articles in the following areas: structure-function relationships of biomolecules; biomolecular recognition, protein-protein and protein-DNA interactions; gene-cloning, genetic engineering, genome analysis, gene targeting, gene expression, vectors, gene therapy; drug targeting, drug design; molecular basis of genetic diseases; conformational studies, computer simulation, novel DNA structures and their biological implications, protein folding; enzymes structure, catalytic mechanisms, regulation; membrane biochemistry, transport, ion channels, signal transduction, cell-cell communication, glycobiology; receptors, antigen-antibody binding, neurochemistry, ageing, apoptosis, cell cycle control; hormones, growth factors; oncogenes, host-virus interactions, viral assembly and structure; intermediary metabolism, molecular basis of disease processes, vitamins, coenzymes, carrier proteins, toxicology; plant and microbial biochemistry; surface forces, micelles and microemulsions, colloids, electrical phenomena, etc. in biological systems. Solicited peer reviewed articles on contemporary Themes and Methods in Biochemistry and Biophysics form an important feature of IJBB. Review articles on a current topic in the above fields are also considered. They must dwell more on research work done during the last couple of years in the field and authors should integrate their own work with that of others with acumen and authenticity, mere compilation of references by a third party is discouraged. While IJBB strongly promotes innovative novel research works for publication as full length papers, it also considers research data emanating from limited objectives, and extension of ongoing experimental works as ‘Notes’. IJBB follows “Double Blind Review process” where author names, affiliations and other correspondence details are removed to ensure fare evaluation. At the same time, reviewer names are not disclosed to authors.