Unknown

Dataset Information

0

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


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.

SUBMITTER: Reich-Slotky R 

PROVIDER: S-EPMC2725597 | BioStudies | 2009-01-01

REPOSITORIES: biostudies

Similar Datasets

2001-01-01 | S-EPMC87346 | BioStudies
2015-01-01 | S-EPMC4309689 | BioStudies
1000-01-01 | S-EPMC3791895 | BioStudies
1999-01-01 | S-EPMC89191 | BioStudies
1999-01-01 | S-EPMC94060 | BioStudies
2011-01-01 | S-EPMC3034610 | BioStudies
2014-01-01 | S-EPMC4139244 | BioStudies
2003-01-01 | S-EPMC1223239 | BioStudies
2013-01-01 | S-EPMC3842914 | BioStudies
2019-01-01 | S-EPMC6916556 | BioStudies