文献类型：期刊文献

英文题名：Sensor histidine kinase is a β-lactam receptor and induces resistance to β-lactam antibiotics

作者：Li, Lu[1];Wang, Qiyao[2];Zhang, Hui[1,3];Yang, Minjun[4];Khan, Mazhar I.[1];Zhou, Xiaohui[1]

机构：[1]Univ Connecticut, Dept Pathobiol & Vet Sci, Storrs, CT 06269 USA;[2]E China Univ Sci & Technol, Sch Biotechnol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[3]Jiangsu Acad Agr Sci, Nanjing 210014, Jiangsu, Peoples R China;[4]Chinese Natl Human Genome Ctr Shanghai, Key Lab Hlth & Dis Genom, Shanghai Minist Sci & Technol MOST, Shanghai 201203, Peoples R China

年份：2016

卷号：113

期号：6

起止页码：1648

外文期刊名：PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000369571700056)】；

基金：We are grateful to Matthew Waldor for insightful comments on the manuscript. This work was supported by the start-up fund from the University of Connecticut, the National Institute of Food and Agriculture, US Department of Agriculture Grant CONS00935 (to X.Z.), and National Natural Science Foundation of China Grants 31372560 and 41376128 (to Q.W.).

语种：英文

外文关键词：Vibrio; histidine kinase; beta-lactam receptor; beta-lactamase

摘要：beta-Lactams disrupt bacterial cell wall synthesis, and these agents are the most widely used antibiotics. One of the principle mechanisms by which bacteria resist the action of beta-lactams is by producing beta-lactamases, enzymes that degrade beta-lactams. In Gram-negative bacteria, production of beta-lactamases is often induced in response to the antibiotic-associated damage to the cell wall. Here, we have identified a previously unidentified mechanism that governs beta-lactamase production. In the Gram-negative enteric pathogen Vibrio parahaemolyticus, we found a histidine kinase/response regulator pair (VbrK/VbrR) that controls expression of a beta-lactamase. Mutants lacking either VbrK or VbrR do not produce the beta-lactamase and are no longer resistant to beta-lactam antibiotics. Notably, VbrK autophosphorylation is activated by beta-lactam antibiotics, but not by other lactams. However, single amino acid substitutions in the putative periplasmic binding pocket of VbrK leads its phosphorylation in response to both beta-lactam and other lactams, suggesting that this kinase is a beta-lactam receptor that can directly detect beta-lactam antibiotics instead of detecting the damage to cell wall resulting from beta-lactams. In strong support of this idea, we found that purified periplasmic sensor domain of VbrK binds penicillin, and that such binding is critical for VbrK autophosphorylation and beta-lactamase production. Direct recognition of beta-lactam antibiotics by a histidine kinase receptor may represent an evolutionarily favorable mechanism to defend against beta-lactam antibiotics.