Abstract
We have studied the mechanism by which β-lactam challenge leads to β-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 β-lactamase through activation of the BlrAB two-component regulatory system. During β-lactam challenge, monomer-disaccharide-pentapeptide levels increase proportionately with β-lactamase production and β-lactamase induction is inhibited by vancomycin, which binds muro-pentapeptides. Taken together, these data strongly suggest that the Aeromonas spp. β-lactamase regulatory sensor kinase, BlrB, responds to the concentration of monomer-disaccharide-pentapeptide in peptidoglycan.