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JAC Advance Access published online on January 22, 2007

Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl510
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Contribution of the Rv2333c efflux pump (the Stp protein) from Mycobacterium tuberculosis to intrinsic antibiotic resistance in Mycobacterium bovis BCG

Santiago Ramón-García1, Carlos Martín1, Edda De Rossi2 and José A. Aínsa1,*

1 Departamento de Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza, 50009 Zaragoza, Spain 2 Dipartimento di Genetica e Microbiologia, Università degli Studi di Pavia, 27100 Pavia, Italy

Received 13 July 2006; returned 17 August 2006; revised 5 November 2006; accepted 21 November 2006


* Corresponding author. Tel: +34-976-762420; Fax: +34-976-762604; E-mail: ainsa{at}unizar.es

OBJECTIVES: To characterize the efflux pump encoded by the gene Rv2333c from Mycobacterium tuberculosis, and assess its contribution to intrinsic antibiotic resistance using Mycobacterium bovis BCG as a model organism.

METHODS: Firstly, the Rv2333c gene was expressed from a multicopy plasmid in M. bovis BCG. Secondly, the gene was inactivated in the chromosome of M. bovis BCG. Antibiotic susceptibility tests and tetracycline uptake/efflux experiments were carried out with the strains mentioned above.

RESULTS: When the Rv2333c gene was inactivated in the M. bovis BCG chromosome, there was a decrease in the MIC values of spectinomycin and tetracycline, and an increase in [3H]tetracycline accumulation. When the Rv2333c gene was cloned into a multicopy plasmid, there was an increase in the MIC values of spectinomycin and tetracycline, and a decrease in [3H]tetracycline accumulation. These results indicate that both antibiotics are substrates of the Rv2333c efflux pump, which has been named Stp, for Spectinomycin Tetracycline efflux Pump.

CONCLUSIONS: The Rv2333c efflux pump (Stp protein) of M. tuberculosis contributes to intrinsic spectinomycin and tetracycline resistance.

Key Words: mycobacteria , spectinomycin , tetracycline , efflux


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