Gemfibrozil inhibits Legionella pneumophila and Mycobacterium tuberculosis enoyl coenzyme A reductases and blocks intracellular growth of these bacteria in macrophages

Ronit Reich-Slotky, Christina A. Kabbash, Phyllis Della-Latta, John S. Blanchard, Steven J. Feinmark, Sherry Freeman, Gilla Kaplan, Howard A. Shuman, Samuel C. Silverstein

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

We report here that gemfibrozil (GFZ) inhibits axenic and intracellular growth of Legionella pneumophila and of 27 strains of wild-type and multidrug-resistant Mycobacterium tuberculosis in bacteriological medium and in human and mouse macrophages, respectively. At a concentration of 0.4 mM, GFZ completely inhibited L. pneumophila fatty acid synthesis, while at 0.12 mM it promoted cytoplasmic accumulation of polyhydroxybutyrate. To assess the mechanism(s) of these effects, we cloned an L. pneumophila FabI enoyl reductase homolog that complemented for growth an Escherichia coli strain carrying a temperature-sensitive enoyl reductase and rendered the complemented E. coli strain sensitive to GFZ at the nonpermissive temperature. GFZ noncompetitively inhibited this L. pneumophila FabI homolog, as well as M. tuberculosis InhA and E. coli FabI.

Original languageEnglish (US)
Pages (from-to)5262-5271
Number of pages10
JournalJournal of Bacteriology
Volume191
Issue number16
DOIs
StatePublished - Aug 1 2009

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Fingerprint Dive into the research topics of 'Gemfibrozil inhibits Legionella pneumophila and Mycobacterium tuberculosis enoyl coenzyme A reductases and blocks intracellular growth of these bacteria in macrophages'. Together they form a unique fingerprint.

  • Cite this