Antimicrobial Agents and Chemotherapy, June 2004, p. 1953-1959, Vol. 48, No. 6
0066-4804/04/$08.00+0 DOI: 10.1128/AAC.48.6.1953-1959.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
tcaA Inactivation Increases Glycopeptide Resistance in Staphylococcus aureus
Hideki Maki,1,
Nadine McCallum,1 Markus Bischoff,1 Akihito Wada,2 and Brigitte Berger-Bächi1*
Department of Medical Microbiology, University of Zürich, CH-8028 Zürich, Switzerland,1
Department of Bacteriology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, 162-8640 Tokyo, Japan2
Received 30 October 2003/
Returned for modification 28 January 2004/
Accepted 21 February 2004
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.
* Corresponding author. Mailing address: Department of Medical Microbiology, University of Zürich, Gloriastr. 32, CH-8028 Zürich, Switzerland. Phone: 41 1 634 2650. Fax: 41 1 634 4906. E-mail: bberger{at}immv.unizh.ch.
Present address: Discovery Research Laboratories, Shionogi & Co., Ltd. 3-1-1, Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
Antimicrobial Agents and Chemotherapy, June 2004, p. 1953-1959, Vol. 48, No. 6
0066-4804/04/$08.00+0 DOI: 10.1128/AAC.48.6.1953-1959.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
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Copyright © 2004 by the American Society for Microbiology. All rights reserved.