ANALYSIS OF PEPTIDOGLYCAN PRECURSORS IN VANCOMYCIN-RESISTANT ENTEROCOCCUS-GALLINARUM BM4174

被引:103
作者
REYNOLDS, PE [1 ]
SNAITH, HA [1 ]
MAGUIRE, AJ [1 ]
DUTKAMALEN, S [1 ]
COURVALIN, P [1 ]
机构
[1] INST PASTEUR,F-75724 PARIS 15,FRANCE
关键词
D O I
10.1042/bj3010005
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Vancomycin resistance in enterococci is an increasing clinical problem, and several phenotypes have been identified. We demonstrate here that the resistance mechanism in the constitutively vancomycin-resistant Enterococcus gallinarum BM4174 involves an altered pathway of peptidoglycan synthesis and hydrolysis of the normal precursors in the vancomycin-sensitive pathway. A ligase encoded by the vanC gene catalyses synthesis of D-Ala-D-Ser and substitutes this dipeptide for D-Ala-D-Ala in peptidoglycan precursors. It is presumed that this substitution lowers the affinity of vancomycin for its target site. Destruction of D-Ala-D-Ala (D,D-peptidase activity) and of UDP-MurNAc-L-Ala-D-isoGlu-L-Lys-D-Ala-D-ala by removal of the terminal D-Ala residue (D,D-carboxypeptidase activity) ensures that the normal vancomycin-sensitive pathway of peptidoglycan synthesis cannot function in the resistant strain.
引用
收藏
页码:5 / 8
页数:4
相关论文
共 17 条
[1]  
ALLEN NE, 1992, FEMS MICROBIOL LETT, V98, P109
[2]   CHARACTERIZATION OF TN1546, A TN3-RELATED TRANSPOSON CONFERRING GLYCOPEPTIDE RESISTANCE BY SYNTHESIS OF DEPSIPEPTIDE PEPTIDOGLYCAN PRECURSORS IN ENTEROCOCCUS-FAECIUM BM4147 [J].
ARTHUR, M ;
MOLINAS, C ;
DEPARDIEU, F ;
COURVALIN, P .
JOURNAL OF BACTERIOLOGY, 1993, 175 (01) :117-127
[3]   GENETICS AND MECHANISMS OF GLYCOPEPTIDE RESISTANCE IN ENTEROCOCCI [J].
ARTHUR, M ;
COURVALIN, P .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1993, 37 (08) :1563-1571
[4]   THE STRUCTURE AND MODE OF ACTION OF GLYCOPEPTIDE ANTIBIOTICS OF THE VANCOMYCIN GROUP [J].
BARNA, JCJ ;
WILLIAMS, DH .
ANNUAL REVIEW OF MICROBIOLOGY, 1984, 38 :339-357
[5]   MODIFICATION OF PEPTIDOGLYCAN PRECURSORS IS A COMMON FEATURE OF THE LOW-LEVEL VANCOMYCIN-RESISTANT VANB-TYPE ENTEROCOCCUS D366 AND OF THE NATURALLY GLYCOPEPTIDE-RESISTANT SPECIES LACTOBACILLUS-CASEI, PEDIOCOCCUS-PENTOSACEUS, LEUCONOSTOC-MESENTEROIDES, AND ENTEROCOCCUS-GALLINARUM [J].
BILLOTKLEIN, D ;
GUTMANN, L ;
SABLE, S ;
GUITTET, E ;
VANHEIJENOORT, J .
JOURNAL OF BACTERIOLOGY, 1994, 176 (08) :2398-2405
[6]   MOLECULAR-BASIS FOR VANCOMYCIN RESISTANCE IN ENTEROCOCCUS-FAECIUM BM4147 - BIOSYNTHESIS OF A DEPSIPEPTIDE PEPTIDOGLYCAN PRECURSOR BY VANCOMYCIN RESISTANCE PROTEINS VANH AND VANA [J].
BUGG, TDH ;
WRIGHT, GD ;
DUTKAMALEN, S ;
ARTHUR, M ;
COURVALIN, P ;
WALSH, CT .
BIOCHEMISTRY, 1991, 30 (43) :10408-10415
[7]   PHENOTYPIC AND GENOTYPIC HETEROGENEITY OF GLYCOPEPTIDE RESISTANCE DETERMINANTS IN GRAM-POSITIVE BACTERIA [J].
DUTKAMALEN, S ;
LECLERCQ, R ;
COUTANT, V ;
DUVAL, J ;
COURVALIN, P .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1990, 34 (10) :1875-1879
[8]   SEQUENCE OF THE VANC GENE OF ENTEROCOCCUS-GALLINARUM BM4174 ENCODING A D-ALANINE - D-ALANINE LIGASE-RELATED PROTEIN NECESSARY FOR VANCOMYCIN RESISTANCE [J].
DUTKAMALEN, S ;
MOLINAS, C ;
ARTHUR, M ;
COURVALIN, P .
GENE, 1992, 112 (01) :53-58
[9]   SEQUENCE OF THE VANB AND DDL GENES ENCODING D-ALANINE-D-LACTATE AND D-ALANINE-D-ALANINE LIGASES IN VANCOMYCIN-RESISTANT ENTEROCOCCUS-FAECALIS V583 [J].
EVERS, S ;
REYNOLDS, PE ;
COURVALIN, P .
GENE, 1994, 140 (01) :97-102
[10]   INDUCIBLE CARBOXYPEPTIDASE ACTIVITY IN VANCOMYCIN-RESISTANT ENTEROCOCCI [J].
GUTMANN, L ;
BILLOTKLEIN, D ;
ALOBEID, S ;
KLARE, I ;
FRANCOUAL, S ;
COLLATZ, E ;
VANHEIJENOORT, J .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1992, 36 (01) :77-80