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Quantitative analysis of the metabolism of soluble cytoplasmic peptidoglycan precursors of glycopeptide‐resistant enterococci
Author(s) -
Arthur Michel,
Depardieu Florence,
Reynolds Peter,
Courvalin Patrice
Publication year - 1996
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.1996.00617.x
Subject(s) - teicoplanin , operon , biology , peptidoglycan , glycopeptide , glycopeptide antibiotic , microbiology and biotechnology , biochemistry , vancomycin , enterococcus faecium , enterococcus faecalis , genetics , gene , bacteria , antibiotics , staphylococcus aureus , escherichia coli
Transposon Tn 1546 from Enterococcus faecium BM4147 mediates high‐level resistance to the glycopeptide antibiotics vancomycin and teicoplanin. Tn 1546 encodes a dehydrogenase (VanH) and a ligase (VanA) that synthesize D ‐alanyl‐ D ‐lactate ( D ‐Ala‐ D ‐Lac), a D D ‐dipeptidase (VanX) that hydrolyses D ‐Ala‐ D ‐Ala and a two‐component regulatory system (VanR–VanS) that controls transcription of the vanHAX operon. Strains of Enterococcus faecalis harbouring various copy numbers of the vanRSHAX cluster were tested to determine if there was a correlation between the levels of resistance to glycopeptides, the levels of expression of the corresponding resistance genes and the relative proportions of the different cytoplasmic peptidoglycan precursors. Increased transcription of the vanHAX operon was associated with increased incorporation of D ‐Ala‐ D ‐Lac into peptidoglycan precursors to the detriment of D ‐Ala‐ D ‐Ala, and with a gradual increase in the vancomycin‐resistance levels. More complete elimination of D ‐Ala‐ D ‐Ala‐containing precursors was required for teicoplanin resistance. The VanY and VanZ proteins also encoded by Tn 1546 were not effectors of the regulation of the vanHAX operon but contributed to vancomycin and teicoplanin resistance, respectively. Differences at the regulatory level accounted for phenotypic diversity in acquired glycopeptide resistance by production of D ‐lac‐ending precursors.