Efflux pump of the proton antiporter family confers low-level fluoroquinolone resistance in Mycobacterium smegmatis

H. E. Takiff, M. Cimino, M. C. Musso, T. Weisbrod, R. Martinez, M. B. Delgado, L. Salazar, B. R. Bloom, W. R. Jacobs

Research output: Contribution to journalArticle

157 Citations (Scopus)

Abstract

Due to the resurgence of tuberculosis and the emergence of multidrug- resistant strains, fluoroquinolones (FQ) are being used in selected tuberculosis patients, but FQ-resistant strains of Mycobacterium tuberculosis have rapidly begun to appear. The mechanisms involved in FQ resistance need to be elucidated if the effectiveness of this class of antibiotics is to be improved and prolonged. By using the rapid-growing Mycobacterium smegmatis as a model genetic system, a gene was selected that confers low-level FQ resistance when present on a multicopy plasmid. This gene, lfrA, encodes a putative membrane efflux pump of the major facilitator family, which appears to recognize the hydrophilic FQ, ethidium bromide, acridine, and some quaternary ammonium compounds. It is homologous to qacA from Staphylococcus aureus, temA, of Streptomyces glaucescens, and actII and mmr, both from Streptomyces coelicoler. Increased expression of lfrA augments the appearance of subsequent mutations to higher-level FQ resistance.

Original languageEnglish (US)
Pages (from-to)362-366
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number1
DOIs
StatePublished - Jan 9 1996

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Antiporters
Mycobacterium smegmatis
Proton Pumps
Fluoroquinolones
Streptomyces
Quaternary Ammonium Compounds
Acridines
Multidrug-Resistant Tuberculosis
Ethidium
Genetic Models
Mycobacterium tuberculosis
Genes
Staphylococcus aureus
Tuberculosis
Plasmids
Anti-Bacterial Agents
Mutation
Membranes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Efflux pump of the proton antiporter family confers low-level fluoroquinolone resistance in Mycobacterium smegmatis. / Takiff, H. E.; Cimino, M.; Musso, M. C.; Weisbrod, T.; Martinez, R.; Delgado, M. B.; Salazar, L.; Bloom, B. R.; Jacobs, W. R.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 1, 09.01.1996, p. 362-366.

Research output: Contribution to journalArticle

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AU - Martinez, R.

AU - Delgado, M. B.

AU - Salazar, L.

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AU - Jacobs, W. R.

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