Role of class A penicillin-binding proteins in the expression of beta-lactam resistance in Enterococcus faecium.
Role of class A penicillin-binding proteins in the expression of beta-lactam resistance in Enterococcus faecium.
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A 类青霉素结合蛋白在屎肠球菌 β-内酰胺耐药性表达中的作用。
DOI：
10.1128/jb.01834-08
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发表时间：
2009
影响因子：
3.2
通讯作者：
Arthur,Michel
中科院分区：
文献类型：
--
作者：
Rice,LouisB;Carias,LenoreL;Rudin,Susan;Hutton,Rebecca;Marshall,Steven;Hassan,Medhat;Josseaume,Nathalie;Dubost,Lionel;Marie,Arul;Arthur,Michel
Peptidoglycan is polymerized by monofunctionald,d-transpeptidases belonging to class B penicillin-binding proteins (PBPs) and monofunctional glycosyltransferases and by bifunctional enzymes that combine both activities (class A PBPs). Three genes encoding putative class A PBPs (pbpF, pbpZ, andponA) were deleted from the chromosome ofEnterococcus faeciumD344R in all possible combinations in order to identify the glycosyltransferases that cooperate with low-affinity class B Pbp5 for synthesis of peptidoglycan in the presence of β-lactam antibiotics. The viability of the triple mutant indicated that glycan strands can be polymerized independently from class A PBPs by an unknown glycosyltranferase. The susceptibility of the ΔpbpFΔponAmutant and triple mutants to extended spectrum cephalosporins (ceftriaxone and cefepime) identified either PbpF or PonA as essential partners of Pbp5 for peptidoglycan polymerization in the presence of the drugs. Mass spectrometry analysis of peptidoglycan structure showed that loss of PonA and PbpF activity led to a minor decrease in the extent of peptidoglycan cross-linking by the remaining PBPs without any detectable compensatory increase in the participation of thel,d-transpeptidase in peptidoglycan synthesis. Optical density measurements and electron microscopy analyses showed that the ΔpbpFΔponAmutant underwent increased stationary-phase autolysis compared to the parental strain. Unexpectedly, deletion of the class Apbpgenes revealed dissociation between the expression of resistance to cephalosporins and penicillins, although the production of Pbp5 was required for resistance to both classes of drugs. Thus, susceptibility of Pbp5-mediated peptidoglycan cross-linking to different β-lactam antibiotics differed as a function of its partner glycosyltransferase.
