title: Distinct roles of major peptidoglycan recycling enzymes in β-Lactamase production in Shewanella oneidensis.
abstract: β-Lactam antibiotics were the earliest discovered and are the most widely used group of antibiotics that work by inactivating penicillin-binding proteins to inhibit peptidoglycan biosynthesis. As one of the most efficient defense strategies, many bacteria produce β-lactam-degrading enzymes, β-lactamases, whose biochemical functions and regulation have been extensively studied. A signal transduction pathway for β-lactamase induction by β-lactam antibiotics, consisting of the major peptidoglycan recycling enzymes and the LysR-type transcriptional regulator, AmpR, has been recently unveiled in some bacteria. Because inactivation of some of these proteins, especially the permease AmpG and the β-hexosaminidase NagZ, results in substantially elevated susceptibility to the antibiotics, these have been recognized as potential therapeutic targets. Here, we show a contrasting scenario in Shewanella oneidensis, in which the homologue of AmpR is absent. Loss of AmpG or NagZ enhances β-lactam resistance drastically, whereas other identified major peptidoglycan recycling enzymes are dispensable. Moreover, our data indicate that there exists a parallel signal transduction pathway for β-lactamase induction, which is independent of either AmpG or NagZ.
authors.affiliation: Institute of Microbiology and College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China Key Laboratory for Agro-Microbial Research and Utilization, Zhejiang Province Hangzhou, Zhejiang, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yin
authors.affiliation: Institute of Microbiology and College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Yinting
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Institute of Microbiology and College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Ju
authors.affiliation: Institute of Microbiology and College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Jin
authors.affiliation: Institute of Microbiology and College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Yiyang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, USA.
authors.forename: Shouguang
authors.initials: S
authors.lastname: Jin
authors.affiliation: Institute of Microbiology and College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China Key Laboratory for Agro-Microbial Research and Utilization, Zhejiang Province Hangzhou, Zhejiang, China haichung@zju.edu.cn.
authors.forename: Haichun
authors.initials: H
authors.lastname: Gao
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects; D055786:Gene Knockout Techniques; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D026901:Membrane Transport Proteins / Q000235:genetics; D008826:Microbial Sensitivity Tests; D046915:Penicillin-Binding Proteins / Q000235:genetics; D010457:Peptidoglycan / Q000096:biosynthesis*; D011401:Promoter Regions, Genetic; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology; D020592:Shewanella / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D018440:beta-Lactam Resistance / Q000235:genetics*; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism; D047090:beta-Lactams / Q000494:pharmacology*; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics
chemical_list: C084284:AmpG protein, Bacteria; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D026901:Membrane Transport Proteins; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan; D047090:beta-Lactams; C071526:AmpR protein, Bacteria; C074160:BlaA protein, Bacteria; D001619:beta-N-Acetylhexosaminidases; D001618:beta-Lactamases