Role of insertion elements and yycFG in the development of decreased susceptibility to vancomycin in Staphylococcus aureus.
The glycopeptide antibiotic vancomycin acts by binding to the D-alanyl-D-alanine terminus of the cell wall precursor lipid II in the cytoplasmic membrane. The purpose of this study was the identification of genes that might be involved in the vancomycin resistance mechanism. To this end, the expression profiles of two vancomycin intermediately resistant Staphylococcus aureus (VISA) strains, the clinical isolate S. aureus SA137/93A (Etest: 8 microg/ml) and its laboratory mutant S. aureus SA137/93G (Etest: 12 microg/ml) were analyzed using an S. aureus full-genome chip. The results indicated that an essential two-component regulatory system, yycF (vicR) and yycG (vicK) was drastically up-regulated in strain SA137/93A. Sequencing of the yycFG promoter region of strain SA137/93A revealed an insertion of IS256 in the predicted promoter region creating a potentially stronger hybrid promoter. In strain SA137/93G, IS256 was not integrated in the yycFG promoter region but, in previous studies, a copy of IS256 had been found to inactivate the tcaA gene (Maki et al. Antimicrob. Agents and Chemother. 48, 1953-1959 (2004)). Detailed population analyses showed that, in addition to the loss of SCCmec, the inactivation of tcaA seems to cause at least part of the increase in teicoplanin and vancomycin resistance in strain SA137/93G.
Jansen
Andrea
A
Institut für Medizinische Mikrobiologie, Immunologie und Parasitologie, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany.
Türck
Michael
M
Szekat
Christiane
C
Nagel
Michael
M
Clever
Indra
I
Bierbaum
Gabriele
G
D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D004251:DNA Transposable Elements; D008969:Molecular Sequence Data; D046915:Penicillin-Binding Proteins / Q000032:analysis; D011401:Promoter Regions, Genetic; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics; D020713:Vancomycin Resistance
D001426:Bacterial Proteins; D004251:DNA Transposable Elements; D046915:Penicillin-Binding Proteins; C119939:YycF protein, Bacteria