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Antimicrob Agents Chemother. 2014 Nov;58(11):6508-17. doi: 10.1128/AAC.03671-14. Epub 2014 Aug 18.

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

Author information

1
Department of Biochemistry and Biomedical Sciences and the Michael G. DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, Ontario, Canada.
2
Department of Biochemistry and Biomedical Sciences and the Michael G. DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, Ontario, Canada burrowl@mcmaster.ca.

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 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-weight d,d-carboxypeptidase. Compared to the wild type, a pbpD1 mutant 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 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.

PMID:
25136010
PMCID:
PMC4249420
DOI:
10.1128/AAC.03671-14
[Indexed for MEDLINE]
Free PMC Article

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