Staphylococcus aureus VRSA-11B is a constitutive vancomycin-resistant mutant of vancomycin-dependent VRSA-11A.
Vancomycin-resistant Staphylococcus aureus VRSA-10 was isolated in 2009, whereas VRSA-11A and VRSA-11B were isolated from the same patient in 2010. Growth curves and determination of the nature of the peptidoglycan precursors and of the VanX d,d-dipeptidase activity in the absence and in the presence of vancomycin indicated that vancomycin resistance was inducible in VRSA-10, that VRSA-11A was partially dependent on glycopeptide for growth, and that VRSA-11B was constitutively resistant. Both VRSA-11A and -11B harbored an insertion sequence, ISEf1, at the same locus in the vanX-vanY intergenic region of Tn1546 and an S(183)A mutation in the chromosomal d-alanyl:d-alanine ligase (Ddl). This substitution has been shown to be responsible for a drastic diminution of the affinity of the enzyme for d-Ala at subsite 1 in Escherichia coli DdlB. VRSA-11B exhibited an additional mutation, P(216)T, in the transcriptional regulator VanR, most probably associated with constitutive expression of vancomycin resistance. It is thus likely that VRSA-11B is a constitutive derivative of VRSA-11A selected during prolonged vancomycin therapy. Synthesis of peptidoglycan precursors ending in d-Ala-d-lactate was responsible for oxacillin susceptibility of VRSA-11A and VRSA-11B despite the presence of a wild-type mecA gene in both strains.
Institut Pasteur, Unité des Agents Antibactériens, Paris, France.
Bruno
B
Périchon
Patrice
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Courvalin
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002268:Carboxypeptidases / Q000235:genetics / Q000378:metabolism; D021901:DNA, Intergenic; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D009154:Mutation; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism; D010457:Peptidoglycan / Q000737:chemistry / Q000378:metabolism*; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase / Q000235:genetics / Q000378:metabolism; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics* / Q000302:isolation & purification* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014640:Vancomycin / Q000494:pharmacology; D020713:Vancomycin Resistance / Q000235:genetics*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D021901:DNA, Intergenic; D008565:Membrane Proteins; D010457:Peptidoglycan; D014157:Transcription Factors; C073902:VanR protein, bacteria; D014640:Vancomycin; D002268:Carboxypeptidases; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase; C117912:VanY protein, Bacteria; C091956:VanX dipeptidase; D010453:Peptide Synthases; C019638:D-alanylalanine synthetase