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Antimicrobial Agents and Chemotherapy, March 2001, p. 800-804, Vol. 45, No. 3
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.3.800-804.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Characterization of P55, a Multidrug Efflux Pump in Mycobacterium bovis and Mycobacterium tuberculosis

Pedro E. A. Silva,1 Fabiana Bigi,2 María de la Paz Santangelo,2 Maria Isabel Romano,2 Carlos Martín,1 Angel Cataldi,2 and José A. Aínsa1,*

Departamento de Microbiología, Medicina Preventiva y Salud Pública, Facultad de Medicina, Universidad de Zaragoza, 50009-Zaragoza, Spain,1 and Instituto de Biotecnología, Centro de Investigaciones en Ciencias Veterinarias (CICV), Instituto Nacional de Tecnología Agropecuaria (INTA), 1708-Moron, Argentina2

Received 23 May 2000/Returned for modification 21 August 2000/Accepted 24 November 2000

The Mycobacterium bovis P55 gene, located downstream from the gene that encodes the immunogenic lipoprotein P27, has been characterized. The gene was identical to the open reading frame of the Rv1410c gene in the genome of Mycobacterium tuberculosis H37Rv, annotated as a probable drug efflux protein. Genes similar to P55 were present in all species of the M. tuberculosis complex and other mycobacteria such as Mycobacterium leprae and Mycobacterium avium. By Western blotting, P55 was located in the membrane fraction of M. bovis. When transformed into Mycobacterium smegmatis after cloning, P55 conferred aminoglycoside and tetracycline resistance. The levels of resistance to streptomycin and tetracycline conferred by P55 were decreased in the presence of the protonophore carbonyl cyanide m-chlorophenylhydrazone and the pump inhibitors verapamil and reserpine. M. smegmatis cells expressing the plasmid-encoded P55 accumulated less tetracycline than the control cells. We conclude that P55 is a membrane protein implicated in aminoglycoside and tetracycline efflux in mycobacteria.

* Corresponding author. Mailing address: Departamento de Microbiología, Medicina Preventiva y Salud Pública, Facultad de Medicina, Universidad de Zaragoza, C/Domingo Miral s/n, 50009-Zaragoza, Spain. Phone: 34-976-762420. Fax: 34-976-761664. E-mail: ainsa{at}posta.unizar.es.

Antimicrobial Agents and Chemotherapy, March 2001, p. 800-804, Vol. 45, No. 3
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.3.800-804.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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