Induction of beta-lactamase production in Aeromonas hydrophila is responsive to beta-lactam-mediated changes in peptidoglycan composition.
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.
Tayler
Amy E
AE
Department of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
Ayala
Juan A
JA
Centro de Biología Molecular 'Severo Ochoa', Consejo Superior de Investigaciones Cientificas, Universidad Autonoma de Madrid, Campus de Cantoblanco, 28049 Madrid, Spain.
Niumsup
Pannika
P
Department of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
Westphal
Katrin
K
Department of Pharmaceutical Microbiology, University of Bonn, 53115 Bonn, Germany.|Department of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
Baker
Jenny A
JA
Department of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
Zhang
Lufei
L
Department of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
Walsh
Timothy R
TR
Department of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
Wiedemann
Bernd
B
Department of Pharmaceutical Microbiology, University of Bonn, 53115 Bonn, Germany.
Bennett
Peter M
PM
Department of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
Avison
Matthew B
MB
Department of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
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*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D010457:Peptidoglycan; D047090:beta-Lactams; D014640:Vancomycin; D001618:beta-Lactamases