title: Induction of beta-lactamase production in Aeromonas hydrophila is responsive to beta-lactam-mediated changes in peptidoglycan composition.
abstract: We have studied the mechanism by which beta-lactam challenge leads to beta-lactamase induction in Aeromonas hydrophila through transposon-insertion mutagenesis. Disruption of the dd-carboxypeptidases/endopeptidases, penicillin-binding protein 4 or BlrY leads to elevated monomer-disaccharide-pentapeptide levels in A. hydrophila peptidoglycan and concomitant overproduction of beta-lactamase through activation of the BlrAB two-component regulatory system. During beta-lactam challenge, monomer-disaccharide-pentapeptide levels increase proportionately with beta-lactamase production and beta-lactamase induction is inhibited by vancomycin, which binds muro-pentapeptides. Taken together, these data strongly suggest that the Aeromonas spp. beta-lactamase regulatory sensor kinase, BlrB, responds to the concentration of monomer-disaccharide-pentapeptide in peptidoglycan.
authors.affiliation: Department of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Tayler
authors.affiliation: Centro de Biología Molecular 'Severo Ochoa', Consejo Superior de Investigaciones Cientificas, Universidad Autonoma de Madrid, Campus de Cantoblanco, 28049 Madrid, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Ayala
authors.affiliation: Department of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Pannika
authors.initials: P
authors.lastname: Niumsup
authors.affiliation: Department of Pharmaceutical Microbiology, University of Bonn, 53115 Bonn, Germany.|Department of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Katrin
authors.initials: K
authors.lastname: Westphal
authors.affiliation: Department of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Jenny A
authors.initials: JA
authors.lastname: Baker
authors.affiliation: Department of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Lufei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Walsh
authors.affiliation: Department of Pharmaceutical Microbiology, University of Bonn, 53115 Bonn, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Wiedemann
authors.affiliation: Department of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Bennett
authors.affiliation: Department of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Avison
mesh_terms: D016980:Aeromonas hydrophila / Q000201:enzymology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism; D016254:Mutagenesis, Insertional; D010457:Peptidoglycan / Q000737:chemistry*; D014640:Vancomycin / Q000494:pharmacology; D001618:beta-Lactamases / Q000096:biosynthesis*; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D010457:Peptidoglycan; D047090:beta-Lactams; D014640:Vancomycin; D001618:beta-Lactamases