Gut Pathogens

While seven penicillin-binding proteins (PBPs) or PBP-like proteins have been identified either by radiolabelled penicillin binding studies or genomic analysis, only PBP3 has been considered of interest for Beta-lactams activity against Listeria monocytogenes. Herein we reveal that both PBP4 and Lmo0441 (a PBP-like protein) play a direct role in cephalosporin activity in L. monocytogenes while PBP4 additionally has a protective affect against both penicillin and carbapenem. Findings The Gram-positive foodborne pathogen Listeria monocytogenes is a causative agent of gastroenteritis [1] and in severe cases, listeriosis, which ranges from a mild flu-like illness to meningitis in non-pregnant individuals, or as infection of the foetus in pregnant women [2]. Ampicillin, either alone or in combination with gentamicin, remains the gold standard treatment for L. monocytogenes infection [3]. Conversely, cephalosporins are usually poorly active and thus not recommended in the treatment of listeriosis [4,5]. This dissociation in susceptibilities between βlactams has been rationalized by the observation that cephalosporins have poor affinity for PBP3 compared to penicillin, suggesting that PBP3 is the primary lethal target for β-lactams in L. monocytogenes [6]. However, at least five different PBPs have been identified in L. monocytogenes based on their ability to bind radioactive penicillin [6,7]. Moreover, genome analysis revealed seven distinct genes with homologies to PBPs in L. monocytogenes [8]. With the exception of pbpB, each of the remaining genes has been disrupted by insertional mutagenesis [9] without loss of cell viability, suggesting that they are not critically required for normal synthesis of cell wall peptidoglycan. Based on a previous study by Guinane et al., [9] in which an increase in the activity of cephalosporins was observed for L. monocytogenes disrupted in lmo2229 and lmo0441, we investigated the role of their corresponding proteins (PBP4 and Lmo0441 respectively) in protecting the pathogen against a penicillin (ampicillin, AMP), a carbapenem (meropenem, MEM) and a cephalosporin (cefuroxime, CFX). The growth rates for wild-type and mutant strains, together with time profiles for the activity of AMP, MEM and CFX at 100 times their MIC were tested over a 24 h period in TSB broth (Fig. 1, left panel). No significant differences in the growth rates were observed between wild type and both mutant strains. However, this effect is only Published: 15 December 2009 Gut Pathogens 2009, 1:23 doi:10.1186/1757-4749-1-23 Received: 3 December 2009 Accepted: 15 December 2009 This article is available from: http://www.gutpathogens.com/content/1/1/23 © 2009 Van de Velde et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Gut Pathogens 2009, 1:23 http://www.gutpathogens.com/content/1/1/23