tcaA inactivation increases glycopeptide resistance in Staphylococcus aureus.
The experimental deletion of the tcaRAB region has been shown to increase teicoplanin resistance in Staphylococcus aureus. By sequential genetic complementation of a tcaRAB mutant, we identified tcaA as the key gene within tcaRAB that is responsible for changes in glycopeptide resistance levels. Northern blot analysis of the tcaRAB region showed that the tcaA gene is expressed only weakly over the growth cycle and is strongly inducible by teicoplanin. Among some clinical isolates tested, glycopeptide-intermediate-resistant (GISA) strains Michigan and SA137/93G were found to have truncated tcaA genes. While the former carries a nucleotide insertion that creates a premature stop codon, the latter was found to harbor an IS256 insertion. Complementation of these two GISA strains with a functional tcaA allele reduced their levels of teicoplanin and vancomycin resistance five- to eightfold and twofold, respectively. The data presented here indicate that inactivation of tcaA contributes to and plays a relevant role in glycopeptide resistance in S. aureus clinical isolates.
Maki
Hideki
H
Department of Medical Microbiology, University of Zürich, Gloriastr. 32, CH-8028 Zürich, Switzerland.
McCallum
Nadine
N
Bischoff
Markus
M
Wada
Akihito
A
Berger-Bächi
Brigitte
B
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial / Q000235:genetics*; D005816:Genetic Complementation Test; D006020:Glycopeptides / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development; D017334:Teicoplanin / Q000494:pharmacology; D014640:Vancomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D017334:Teicoplanin; D014640:Vancomycin