Moubareck C, Meziane-Cherif D, Courvalin P, Périchon B
VanA-type Staphylococcus aureus VRSA-7 is Partially Dependent on Vancomycin for Growth. [JOURNAL ARTICLE]
Antimicrob Agents Chemother 2009 Jun 15.
VanA-type Staphylococcus aureus VRSA-7 was partially dependent on glycopeptides for growth. The vanA gene cluster, together with the erm(A) and ant(9)-Ia resistance genes, was carried by the ca. 35-40 kb conjugative plasmid pIP848 present at five copies per cell. The chromosomal ddl gene had a mutation leading to a N308K substitution in the D-Ala:D-Ala ligase that resulted in a 1000-fold decrease in activity relative to that of the VRSA-6 strain. Strain VRSA-7 grown in the absence or in the presence of vancomycin synthesized mainly precursors ending in D-Ala-D-Lac indicating that the strain relied on the vancomycin resistance pathway for peptidoglycan synthesis. Greatly enhanced growth in the presence of glycopeptides and absence of mutations in VanR/VanS indicated inducible expression of resistance. Thus, a combination of loose regulation of the vanA operon by the two-component system together with a gene dosage effect accounts for partial glycopeptide dependence of VRSA-7. Since D-Ala-D-Lac ending peptidoglycan precursors are not processed by PBP2', the strain was fully susceptible to oxacillin despite the production of a wild-type PBP2'.
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