In terms of the reaction with ОІ-lactam antibiotics, for both PBPs and ОІ-lactamases, in the first acylation step, the active-site serine attacks the ОІ-lactam ring present in these antibiotics forming a covalent acyl-enzyme complex. The resistance-causing ОІ-lactamases of class A, C and D contain the same three specific functional motifs and also employ an active-site serine residue to turn over ОІ-lactam antibiotics. These reactions are mediated by three specific functional motifs: SXXK, (S/Y)XN and (K/H)(S/T)G. Usually, these enzymes are acyl-serine transferases that catalyze their reactions by employing an active-site serine moiety as a nucleophile to attack the acyl-D-Ala-D-Ala portion of the peptidoglycan. The penicillin-binding domains of PBPs function as DD-transpeptidases, which catalyze the final step of cell wall biosynthesis by cross-linking two strands of peptidoglycan, or DD-peptidases, which remove the C-terminal D-alanine from the peptidoglycan. These proteins are referred as PBPs due to their ability to bind to ОІ-lactam antibiotics, and based on their molecular weights, PBPs can be classified into two groups: low molecular weight PBPs and high molecular weight PBPs, each of which is subdivided into three classes based on amino-acid sequence similarities. Penicillin-binding proteins (PBPs) are a family of enzymes that are responsible for the polymerization of the glycan strand and the cross-linking between glycan chains. The bacterial peptidoglycan, a three-dimensional, net-like mesh, is the major constituent of the cell wall. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Д¬ompeting interests: The authors have declared that no competing interests exist. All data are included within the manuscript.ДЇunding: This work was supported by grants from the Swedish Research Council to DIA (grant 2012вЂ“3482) and MS (grant 2013вЂ“5930). This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Дata Availability: The authors confirm that all data underlying the findings are fully available without restriction. Received: MaAccepted: ApPublished: May 8, 2014Д¬opyright: В© 2014 Sun et al. PLoS ONE 9(5):Д®ditor: Axel Cloeckaert, Institut National de la Recherche Agronomique, France

Our results suggest that: (i) most evolved PBPs became вЂgeneralistsвЂќ with increased resistance against several different classes of ОІ-lactam antibiotics, (ii) synergistic interactions between mutations conferring antibiotic resistance are common and (iii) the mechanism of resistance of these mutants could be to make the active site more accessible for water allowing hydrolysis or less binding to ОІ-lactam antibiotics.Д¬itation: Sun S, Selmer M, Andersson DI (2014) Resistance to ОІ-Lactam Antibiotics Conferred by Point Mutations in Penicillin-Binding Proteins PBP3, PBP4 and PBP6 in Salmonella enterica.

We could after mutagenesis and selection in presence of penicillin G isolate mutants with amino-acid substitutions in the PBPs, FtsI, DacB and DacC (corresponding to PBP3, PBP4 and PBP6) with increased resistance against ОІ-lactam antibiotics. As no systematic studies have been performed to examine the potential of all PBPs present in one bacterial species to evolve increased resistance against ОІ-lactam antibiotics, we explored the ability of fifteen different defined or putative PBPs in Salmonella enterica to acquire increased resistance against penicillin G. Mutational alterations in PBPs can confer resistance either by reducing binding of the antibiotic to the active site or by evolving a ОІ-lactamase activity that degrades the antibiotic. Penicillin-binding proteins (PBPs) are enzymes responsible for the polymerization of the glycan strand and the cross-linking between glycan chains as well as the target proteins for ОІ-lactam antibiotics.

Pbp3 gene and legionella