文献类型：期刊文献

英文题名：Analysis of AcrB in Klebsiella pneumoniae reveals natural variants promoting enhanced multidrug resistance

作者：Li, Ying[1,2];Cross, Trevor S.[1,3];Dorr, Tobias[1,3]

第一作者：Li, Ying;李映

通讯作者：Dorr, T[1];Li, Y[2]

机构：[1]Cornell Univ, Weill Inst Cell & Mol Biol, Ithaca, NY 14853 USA;[2]Beijing Union Univ, Coll Biochem Engn, Beijing 100023, Peoples R China;[3]Cornell Univ, Dept Microbiol, Ithaca, NY 14853 USA

第一机构：Cornell Univ, Weill Inst Cell & Mol Biol, Ithaca, NY 14853 USA

通讯机构：[1]corresponding author), Cornell Univ, Weill Inst Cell & Mol Biol, Ithaca, NY 14853 USA;[2]corresponding author), Beijing Union Univ, Coll Biochem Engn, Beijing 100023, Peoples R China.|[1141726]北京联合大学生物化学工程学院;[11417]北京联合大学;

年份：2022

卷号：173

期号：3

外文期刊名：RESEARCH IN MICROBIOLOGY

收录：;Scopus(收录号：2-s2.0-85127343819);WOS:【SCI-EXPANDED(收录号:WOS:000793468900008)】；

基金：Research on antibiotic tolerance in the Dorr laboratory is sup-ported by NIH grant R01AI143704; Dr. Ying Li was supported by China Scholarship Council fellowship 201908110070.

语种：英文

外文关键词：AcrAB; Efflux pump; Resistance-nodulation-cell division; Antibiotic resistance

摘要：Infections caused by Klebsiella pneumoniae are often difficult to manage due to the high frequency of multidrug resistance, often conferred by efflux pumps. In this study, we analyzed sequence variations of the major RND family multidrug efflux pump AcrB from 387 assembled K. pneumoniae genomes. We confirm that AcrB is a highly-conserved efflux pump in K. pneumoniae, and identified several variants that were prevalent in clinical isolates. Molecular dynamics analyses on two of these variants (L118M and S966A) suggested conformational changes that may correlate with increased drug efflux capabilities. The L118M change resulted in enhanced protein rigidity while the flexibility of drug binding pockets was stable or increased, and the interactions between the proximal pockets and water molecules were stronger. For S966A, the significantly enlarged proximal pocket suggested higher drug accommodation ability. Consistent with these predictions, the L118M and S966A variants conferred a slightly increased ability to grow in the presence of tetracycline and to survive cefoxitin exposure when overexpressed. In summary, our results suggest that the emergence of enhanced-function AcrB variants may be a potential risk for increased antibiotic resistance in clinical K. pneumoniae isolates. (c) 2021 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.