title: PBP1a/LpoA but not PBP1b/LpoB are involved in regulation of the major β-lactamase gene blaA in Shewanella oneidensis.
abstract: β-Lactamase production is one of the most important strategies for Gram-negative bacteria to combat β-lactam antibiotics. Studies of the regulation of β-lactamase expression have largely been focused on the class C β-lactamase AmpC, whose induction by β-lactams requires LysR-type regulator AmpR and permease AmpG-dependent peptidoglycan recycling intermediates. In Shewanella, which is ubiquitous in aquatic environments and is a reservoir for antibiotic resistance, production of the class D β-lactamase BlaA confers bacteria with natural resistance to many β-lactams. Expression of the blaA gene in the genus representative Shewanella oneidensis is distinct from the AmpC paradigm because of the lack of an AmpR homologue and the presence of an additional AmpG-independent regulatory pathway. In this study, using transposon mutagenesis, we identify proteins that are involved in blaA regulation. Inactivation of mrcA and lpoA, which encode penicillin binding protein 1a (PBP1a) and its lipoprotein cofactor, LpoA, respectively, drastically enhances blaA expression in the absence of β-lactams. Although PBP1b and its cognate, LpoB, also exist in S. oneidensis, their roles in blaA induction are dispensable. We further show that the mrcA-mediated blaA expression is independent of AmpG.
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 Key Laboratory for Agro-Microbial Research and Utilization, Zhejiang Province, Hangzhou, Zhejiang, China.
authors.forename: Yiyang
authors.initials: Y
authors.lastname: Sun
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: Yinting
authors.initials: Y
authors.lastname: Mao
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: Miao
authors.initials: M
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*; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D046915:Penicillin-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020592:Shewanella / Q000187:drug effects* / Q000201:enzymology*; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D001426:Bacterial Proteins; D046915:Penicillin-Binding Proteins; D047090:beta-Lactams; C048795:AmpC beta-lactamases; D001618:beta-Lactamases
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