Role of PBPD1 in stimulation of Listeria monocytogenes biofilm formation by subminimal inhibitory ?-lactam concentrations.

ABSTRACT: Disinfectant-tolerant Listeria monocytogenes biofilms can colonize surfaces that come into contact with food, leading to contamination and, potentially, food-borne illnesses. To better understand the process of L. monocytogenes biofilm formation and dispersal, we screened 1,120 off-patent FDA-approved drugs and identified several that modulate Listeria biofilm development. Among the hits were more than 30 ?-lactam antibiotics, with effects ranging from inhibiting (?50%) to stimulating (?200%) biofilm formation compared to control. Most ?-lactams also dispersed a substantial proportion of established biofilms. This phenotype did not necessarily involve killing, as >50% dispersal could be achieved with concentrations as low as 1/20 of the MIC of some cephalosporins. Penicillin-binding protein (PBP) profiling using a fluorescent penicillin analogue showed similar inhibition patterns for most ?-lactams, except that biofilm-stimulatory drugs did not bind PBPD1, a low-molecular-weight d,d-carboxypeptidase. Compared to the wild type, a pbpD1 mutant had an attenuated biofilm response to stimulatory ?-lactams. The cephalosporin-responsive CesRK two-component regulatory system, whose regulon includes PBPs, was not required for the response. The requirement for PBPD1 activity for ?-lactam stimulation of L. monocytogenes biofilms shows that the specific set of PBPs that are inactivated by a particular drug dictates whether a protective biofilm response is provoked.

SUBMITTER: Nguyen UT 

PROVIDER: S-EPMC4249420 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature