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Antimicrobial Agents and Chemotherapy, December 2001, p. 3387-3392, Vol. 45, No. 12
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.12.3387-3392.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Intrinsic Resistance of Mycobacterium smegmatis to Fluoroquinolones May Be Influenced by New Pentapeptide Protein MfpA

Clemente Montero,dagger Guaniri Mateu, Rosalva Rodriguez, and Howard Takiff*

Laboratorio de Genética Molecular, Centro de Microbiología y Biología Celular, Instituto de Investigaciones Cientificas (IVIC), Caracas 1020A, Venezuela

Received 18 April 2001/Returned for modification 27 June 2001/Accepted 14 August 2001

The fluoroquinolones (FQ) are used in the treatment of Mycobacterium tuberculosis, but the development of resistance could limit their effectiveness. FQ resistance (FQR) is a multistep process involving alterations in the type II topoisomerases and perhaps in the regulation of efflux pumps, but several of the steps remain unidentified. Recombinant plasmid pGADIV was selected from a genomic library of wild-type (WT), FQ-sensitive M. smegmatis by its ability to confer low-level resistance to sparfloxacin (SPX). In WT M. smegmatis, pGADIV increased the MICs of ciprofloxacin (CIP) by fourfold and of SPX by eightfold, and in M. bovis BCG it increased the MICs of both CIP and SPX by fourfold. It had no effect on the accumulation of 14C-labeled CIP or SPX. The open reading frame responsible for the increase in FQR, mfpA, encodes a putative protein belonging to the family of pentapeptides, in which almost every fifth amino acid is either leucine or phenylalanine. Very similar proteins are also present in M. tuberculosis and M. avium. The MICs of CIP and SPX were lower for an M. smegmatis mutant strain lacking an intact mfpA gene than for the WT strain, suggesting that, by some unknown mechanism, the gene product plays a role in determining the innate level of FQR in M. smegmatis.

* Corresponding author. Mailing address: Laboratorio de Genética Molecular, Centro de Microbiología y Biología Celular, Instituto de Investigaciones Cientificas (IVIC), Apdo. 21827, Caracas 1020A, Venezuela. Phone: 58 212 504 1439. Fax: 58 212 504 1499. E-mail: htakiff{at}ivic.ve.

dagger Present address: Department of Chemical Engineering, North Carolina State University, Raleigh, N.C.

Antimicrobial Agents and Chemotherapy, December 2001, p. 3387-3392, Vol. 45, No. 12
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.12.3387-3392.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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