Mutated response regulator graR is responsible for phenotypic conversion of Staphylococcus aureus from heterogeneous vancomycin-intermediate resistance to vancomycin-intermediate resistance

Hui Min Neoh, Longzhu Cui, Harumi Yuzawa, Fumihiko Takeuchi, Miki Matsuo, Keiichi Hiramatsu

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Multistep genetic alteration is required for methicillin-resistant Staphylococcus aureus (MRSA) to achieve the level of vancomycin resistance of vancomycin-intermediate S. aureus (VISA). In the progression of vancomycin resistance, strains with heterogeneous vancomycin resistance, designated hetero-VISA, are observed. In studying the whole-genome sequencing of the representative hetero-VISA strain Mu3 and comparing it with that of closely related MRSA strains Mu50 (VISA) and N315 (vancomycin-susceptible S. aureus [VSSA]), we identified a mutation in the response regulator of the graSR two-component regulatory system. Introduction of mutated graR, designated graR*, but not intact graR, designated graRn, could convert the hetero-VISA phenotype of Mu3 into a VISA phenotype which was comparable to that of Mu50. The same procedure did not appreciably increase the vancomycin resistance of VSSA strain N315, indicating that graR* expression was effective only in the physiological milieu of hetero-VISA cell to achieve a VISA phenotype. Interestingly, the overexpression of graR* increased the daptomycin MICs in both Mu3 and N315 and decreased the oxacillin MIC in N315.

Original languageEnglish
Pages (from-to)45-53
Number of pages9
JournalAntimicrobial Agents and Chemotherapy
Volume52
Issue number1
DOIs
Publication statusPublished - Jan 2008
Externally publishedYes

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Vancomycin Resistance
Vancomycin
Staphylococcus aureus
Methicillin-Resistant Staphylococcus aureus
Phenotype
Daptomycin
Oxacillin
Genome

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Mutated response regulator graR is responsible for phenotypic conversion of Staphylococcus aureus from heterogeneous vancomycin-intermediate resistance to vancomycin-intermediate resistance. / Neoh, Hui Min; Cui, Longzhu; Yuzawa, Harumi; Takeuchi, Fumihiko; Matsuo, Miki; Hiramatsu, Keiichi.

In: Antimicrobial Agents and Chemotherapy, Vol. 52, No. 1, 01.2008, p. 45-53.

Research output: Contribution to journalArticle

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