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Gemfibrozil Inhibits Legionella pneumophila and Mycobacterium tuberculosis Enoyl Coenzyme A Reductases and Blocks Intracellular Growth of These Bacteria in Macrophages

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

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.

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Also Published In

Title
Journal of Bacteriology
DOI
https://doi.org/10.1128/JB.00175-09

More About This Work

Academic Units
Physiology and Cellular Biophysics
Pharmacology
Microbiology and Immunology
Pathology and Cell Biology
Publisher
American Society for Microbiology
Published Here
January 7, 2016