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Staphylococcus aureus VRSA-11B Is a Constitutive Vancomycin-Resistant Mutant of Vancomycin-Dependent VRSA-11A

Bruno Périchon 1 Patrice Courvalin 1, *
* Corresponding author
Abstract : ABSTRACT 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, IS Ef1 , at the same locus in the vanX-vanY intergenic region of Tn 1546 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.
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Submitted on : Wednesday, June 16, 2021 - 4:53:14 PM
Last modification on : Tuesday, July 20, 2021 - 3:30:17 PM

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Bruno Périchon, Patrice Courvalin. Staphylococcus aureus VRSA-11B Is a Constitutive Vancomycin-Resistant Mutant of Vancomycin-Dependent VRSA-11A. Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2012, 56 (9), pp.4693-4696. ⟨10.1128/AAC.00454-12⟩. ⟨pasteur-03262725⟩

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