Role of PBPD1 in Stimulation of Listeria monocytogenes Biofilm Formation by Subminimal Inhibitory β-Lactam Concentrations Academic Article uri icon

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abstract

  • ABSTRACTDisinfectant-tolerantListeria monocytogenesbiofilms can colonize surfaces that come into contact with food, leading to contamination and, potentially, food-borne illnesses. To better understand the process ofL. monocytogenesbiofilm formation and dispersal, we screened 1,120 off-patent FDA-approved drugs and identified several that modulateListeriabiofilm development. Among the hits were more than 30 β-lactam antibiotics, with effects ranging from inhibiting (≤50%) to stimulating (≥200%) biofilm formation compared to control. Most β-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 β-lactams, except that biofilm-stimulatory drugs did not bind PBPD1, a low-molecular-weightd,d-carboxypeptidase. Compared to the wild type, apbpD1mutant had an attenuated biofilm response to stimulatory β-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 β-lactam stimulation ofL. monocytogenesbiofilms shows that the specific set of PBPs that are inactivated by a particular drug dictates whether a protective biofilm response is provoked.

publication date

  • November 2014

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