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

Journal of Bacteriology

Volumn 191, Issue 16, 2009, Pages 5262-5271

  Reich Slotky, Ronit ^a   Kabbash, Christina A ^a   Della Latta, Phyllis ^a   Blanchard, John S ^b   Feinmark, Steven J ^a   Freeman, Sherry ^c   Kaplan, Gilla ^c   Shuman, Howard A ^a   Silverstein, Samuel C ^a,d  

^a NewYork Presbyterian Hospital   (United States)

^b ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^c PUBLIC HEALTH RESEARCH INSTITUTE   (United States)

^d Columbia University ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACYL COENZYME A DEHYDROGENASE (NADP); BACTERIAL PROTEIN; BEZAFIBRATE; CHLORAMPHENICOL; CIPROFLOXACIN; CLOFIBRATE; COENZYME A; ETHAMBUTOL; GEMFIBROZIL; ISONIAZID; KANAMYCIN; OFLOXACIN; POLY(3 HYDROXYBUTYRIC ACID); PROTEIN FABI; PROTEIN INHA; RIFAMPICIN; STREPTOMYCIN; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBACTERIAL ACTIVITY; ARTICLE; COMPETITIVE INHIBITION; CONCENTRATION RESPONSE; CONTROLLED STUDY; ENZYME INHIBITION; FATTY ACID SYNTHESIS; GROWTH INHIBITION; HUMAN; HUMAN CELL; LEGIONELLA PNEUMOPHILA; MACROPHAGE ACTIVATION; MOLECULAR CLONING; MOUSE; MULTIDRUG RESISTANCE; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; NUCLEOTIDE SEQUENCE; PERITONEUM MACROPHAGE; PRIORITY JOURNAL; STRAIN IDENTIFICATION; TEMPERATURE SENSITIVITY; WILD TYPE;

ACYL-COA DEHYDROGENASES; AMINO ACID SEQUENCE; ANIMALS; CELLS, CULTURED; CLOFIBRIC ACID; ENZYME ACTIVATION; ESCHERICHIA COLI; GEMFIBROZIL; GLYCERALDEHYDE; HUMANS; KINETICS; LEGIONELLA PNEUMOPHILA; LIPID METABOLISM; MACROPHAGES; MICE; MICROBIAL SENSITIVITY TESTS; MICROSCOPY, ELECTRON, TRANSMISSION; MOLECULAR SEQUENCE DATA; MYCOBACTERIUM TUBERCULOSIS; PROPANE; SEQUENCE HOMOLOGY, AMINO ACID;

ESCHERICHIA COLI; LEGIONELLA PNEUMOPHILA; MYCOBACTERIUM TUBERCULOSIS;

EID: 67749099414     PISSN: 00219193     EISSN: None     Source Type: Journal    
DOI: 10.1128/JB.00175-09     Document Type: Article

References (58)

1. Babel, W., J. U. Ackermann, and U. Breuer. 2001. Physiology, regulation, and limits of the synthesis of poly(3HB). Adv. Biochem. Eng. Biotechnol. 71:125-157.
2. Banerjee, A., E. Dubnau, A. Quemard, V. Balasubramanian, K. S. Um, T. Wilson, D. Collins, G. de Lisle, and W. R. Jacobs, Jr. 1994. inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science 263:227-230.
3. Bergler, H., S. Fuchsbichler, G. Hogenauer, and F. Turnowsky. 1996. The enoyl-[acyl-carrier-protein] reductase (FabI) of Escherichia coli, which catalyzes a key regulatory step in fatty acid biosynthesis, accepts NADH and NADPH as cofactors and is inhibited by palmitoyl-CoA. Eur. J. Biochem. 242:689-694.
4. Bergler, H., P. Wallner, A. Ebeling, B. Leitinger, S. Fuchsbichler, H. Aschauer, G. Kollenz, G. Högenauer, and F. Turnowsky. 1994. Protein EnvM is the NADH-dependent enoyl-ACP reductase (FabI) of Escherichia coli. J. Biol. Chem. 269:5493-5496.
5. Bligh, E. G., and W. J. Dyer. 1959. A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 37:911-917.
6. Bloch, K. 1977. Control mechanisms for fatty acid synthesis in Mycobacterium smegmatis. Adv. Enzymol. Relat. Areas Mol. Biol. 45:1-84.
7. Brennan, P. J. 2003. Structure, function, and biogenesis of the cell wall of Mycobacterium tuberculosis. Tuberculosis (Edinburgh) 83:91-97.
8. Bronfman, M., M. N. Morales, L. Amigo, A. Orellana, L. Nunez, L. Cardenas, and P. C. Hidalgo. 1992. Hypolipidaemic drugs are activated to acyl-CoA esters in isolated rat hepatocytes. Detection of drug activation by human liver homogenates and by human platelets. Biochem. J. 284:289-295.
9. Chandler, F. W., R. M. Cole, M. D. Hicklin, J. A. Blackmon, and B. S. Callaway. 1979. Ultrastructure of the Legionnaire's disease bacterium. Ann. Int. Med. 90:642-647.
10. Chien, M., I. Morozova, S. Shi, H. Sheng, J. Chen, S. M. Gomez, G. Asamani, K. Hill, J. Nuara, M. Feder, J. Rineer, J. J. Greenberg, V. Steshenko, S. H. Park, B. Zhao, E. Teplitskaya, J. R. Edwards, S. Pampou, A. Georghiou, I. C. Chou, W. Iannuccilli, M. E. Ulz, D. H. Kim, A. Geringer-Sameth, C. Goldsberry, P. Morozov, S. G. Fischer, G. Segal, X. Qu, A. Rzhetsky, P. Zhang, E. Cayanis, P. J. De Jong, J. Ju, S. Kalachikov, H. A. Shuman, and J. J. Russo. 2004. The genomic sequence of the accidental pathogen Legionella pneumophila. Science 305:1966-1968.
11. Drogemuller, C. J., S. Nunthasomboon, and K. M. Knights. 2001. Nafenopin-, ciprofibroyl-, and palmitoyl-CoA conjugation in vitro: kinetic and molecular characterization of marmoset liver microsomes and expressed MLCL1. Arch. Biochem. Biophys. 396:56-64.
12. Feeley, J. C., R. J. Gibson, G. W. Gorman, N. C. Langford, J. K. Rasheed, D. C. Mackel, and W. B. Baine. 1979. Charcoal-yeast extract agar: primary isolation medium for Legionella pneumophila. J. Clin. Microbiol. 10:437-441.
13. Ferrandez, A., B. Minambres, B. Garcia, E. R. Olivera, J. M. Luengo, J. L. Garcia, and E. Diaz. 1998. Catabolism of phenylacetic acid in Escherichia coli. Characterization of a new aerobic hybrid pathway. J. Biol. Chem. 273:25974-25986.
14. Fortier, A. H., and L. A. Falk. 2002. Isolation of murine macrophages. In J. E. Coligan, A. M. Kruisbeek, D. M. Margulies, E. M. Shevach, and W. Strober (ed.), Current protocols in immunology. John Wiley and Sons, New York, NY [Book online.] 14. Unit 14.1. Basic protocol 2. http://www.mrw2.interscience.wiley.com/cponline/tserver.dll?command= doGetDoc&sUI=&database=CP&useScheme=WIS-Framed.Scheme&getDoc= cp-cpim-fs.html.
15. Freeman, S., F. A. Post, L. G. Bekker, R. Harbacheuski, L. M. Steyn, B. Ryffel, N. D. Connell, B. N. Kreiswirth, and G. Kaplan. 2006. Mycobacterium tuberculosis H37Ra and H37Rv differential growth and cytokine/chemokine induction in murine macrophages in vitro. J. Interferon Cytokine Res. 26:27-33.
16. Gobel, M., K. Kassel-Cati, E. Schmidt, and W. Reineke. 2002. Degradation of aromatics and chloroaromatics by Pseudomonas sp. strain B13: cloning, characterization, and analysis of sequences encoding 3-oxoadipate:succinylcoenzyme A (CoA) transferase and 3-oxoadipyl-CoA thiolase. J. Bacteriol. 184:216-223.
17. Hankermeyer, C. R., and R. S. Tjeerdema. 1999. Polyhydroxybutyrate: plastic made and degraded by microorganisms. Rev. Environ. Contam. Toxicol. 159:1-24.
18. Heath, R. J., and C. O. Rock. 1995. Enoyl-acyl carrier protein reductase (fabI) plays a determinant role in completing cycles of fatty acid elongation in Escherichia coli. J. Biol. Chem. 270:26538-26542.
19. Heath, R. J., and C. O. Rock. 1996. Regulation of fatty acid elongation and initiation by acyl-acyl carrier protein in Escherichia coli. J. Biol. Chem. 271:1833-1836.
20. Heath, R. J., S. W. White, and C. O. Rock. 2002. Inhibitors of fatty acid synthesis as antimicrobial chemotherapeutics. Appl. Microbiol. Biotechnol. 58:695-703.
21. Heath, R. J., S. W. White, and C. O. Rock. 2001. Lipid biosynthesis as a target for antibacterial agents. Prog. Lipid Res. 40:467-497.
22. Heath, R. J., Y. T. Yu, M. A. Shapiro, E. Olson, and C. O. Rock. 1998. Broad spectrum antimicrobial biocides target the FabI component of fatty acid synthesis. J. Biol. Chem. 273:30316-30320.
23. Hemmingway, C. J., K. K. Tey, and M. R. Munday. 1995. Short-term inhibition of fatty acid and cholesterol biosynthesis by the lipid lowering drug gemfibrozil in primary rat hepatocyte cultures and rat liver in vivo. Biochem. Soc. Trans. 23:496S.
24. Horwitz, M. A. 1983. Formation of a novel phagosome by the Legionnaires' disease bacterium (Legionella pneumophila) in human monocytes. J. Exp. Med. 158:1319-1331.
25. Horwitz, M. A. 1983. The Legionnaires' disease bacterium (Legionella pneumophila) inhibits phagosome-lysosome fusion in human monocytes. J. Exp. Med. 158:2108-2126.
26. Horwitz, M. A. 1984. Phagocytosis of the Legionnaires' disease bacterium (Legionella pneumophila) occurs by a novel mechanism: engulfment within a pseudopod coil. Cell 36:27-33.
27. Horwitz, M. A. 1983. Symbiotic interactions between Legionella pneumophila and human leukocytes. Int. Rev. Cytol. 14(Suppl.):307- 328.
28. Horwitz, M. A., and S. C. Silverstein. 1983. Intracellular multiplication of Legionnaires' disease bacteria (Legionella pneumophila) in human monocytes is reversibly inhibited by erythromycin and rifampin. J. Clin. Investig. 71:15-26.
29. James, B. W., W. S. Mauchline, P. J. Dennis, C. W. Keevil, and R. Wait. 1999. Poly-3-hydroxybutyrate in Legionella pneumophila, an energy source for survival in low-nutrient environments. Appl. Environ. Microbiol. 65:822-827.
30. Jin, F. Y., V. S. Kamanna, M. Y. Chuang, K. Morgan, and M. L. Kashyap. 1996. Gemfibrozil stimulates apolipoprotein A-I synthesis and secretion by stabilization of mRNA transcripts in human hepatoblastoma cell line (Hep G2). Arterioscler. Thromb. Vasc. Biol. 16:1052-1062.
31. Kabbash, C. A. 2000. Characterization of gemfibrozil's novel mechanism of antibacterial action. Ph.D. dissertation. Columbia University, New York, NY.
32. Kawaguchi, K., Y. Shinoda, H. Yurimoto, Y. Sakai, and N. Kato. 2006. Purification and characterization of benzoate-CoA ligase from Magnetospirillum sp. strain TS-6 capable of aerobic and anaerobic degradation of aromatic compounds. FEMS Microbiol. Lett. 257:208-213.
33. Mahapatra, K., M. S. Kumar, and T. Chakrabarti. 2007. Production and recovery process of polyhydroxybutyrate (PHB) from waste activated sludge. J. Environ. Sci. Eng. 49:164-169.
34. Manca, C., S. Paul, C. E. Barry III, V. H. Freedman, and G. Kaplan. 1999. Mycobacterium tuberculosis catalase and peroxidase activities and resistance to oxidative killing in human monocytes in vitro. Infect. Immun. 67:74-79.
35. Manca, C., L. Tsenova, A. Bergtold, S. Freeman, M. Tovey, J. M. Musser, C. E. Barry III, V. H. Freedman, and G. Kaplan. 2001. Virulence of a Mycobacterium tuberculosis clinical isolate in mice is determined by failure to induce Th1 type immunity and is associated with induction of IFN-alpha/ beta. Proc. Natl. Acad. Sci. USA 98:5752-5757.
36. Mauchline, W. S., and C. W. Keevil. 1991. Development of the BIOLOG substrate utilization system for identification of Legionella spp. Appl. Environ. Microbiol. 57:3345-3349.
37. Munoz-Elias, E. J., and J. D. McKinney. 2005. Mycobacterium tuberculosis isocitrate lyases 1 and 2 are jointly required for in vivo growth and virulence. Nat. Med. 11:638-644.
38. Niederweis, M. 2008. Nutrient acquisition by mycobacteria. Microbiology 154:679-692.
39. Ostle, A. G., and J. G. Holt. 1982. Nile blue A as a fluorescent stain for poly-β hydroxybutyrate. Appl. Environ. Microbiol. 44:238-241.
40. Riis, W., and W. Mai. 1988. Gas chromatographic determination of poly-β-hydroxybutyric acid in microbial biomass after hydrochloric acid propanolysis. J. Chromatogr. 445:285-289.
41. Rock, C. O., J. L. Garwin, and J. E. Cronan, Jr. 1981. Preparative enzymatic synthesis of acyl-acyl carrier protein. Methods Enzymol. 72:397-403.
42. Rodgers, F. G., and M. R. Davey. 1982. Ultrastructure of the cell envelope layers and surface details of Legionella pneumophila. J. Gen. Microbiol. 128:1547-1557.
43. Rozwarski, D. A., G. A. Grant, D. H. Barton, W. R. Jacobs, Jr., and J. C. Sacchettini. 1998. Modification of the NADH of the isoniazid target (InhA) from Mycobacterium tuberculosis. Science 279:98-102.
44. Rozwarski, D. A., C. Vilcheze, M. Sugantino, R. Bittman, and J. C. Sacchettini. 1999. Crystal structure of the Mycobacterium tuberculosis enoyl-ACP reductase, InhA, in complex with NAD+ and a C16 fatty acyl substrate. J. Biol. Chem. 274:15582-15589.
45. Rudin, D. E., P. X. Gao, C. X. Cao, H. C. Neu, and S. C. Silverstein. 1992. Gemfibrozil enhances the listeriacidal effects of fluoroquinolone antibiotics in J774 macrophages. J. Exp. Med. 176:1439-1447.
46. Sadosky, A. B., L. A. Wiater, and H. A. Shuman. 1993. Identification of Legionella pneumophila genes required for growth within and killing of human macrophages. Infect. Immun. 61:5361-5373.
47. Sanchez, R. M., M. Vinals, M. Alegret, M. Vazquez, T. Adzet, M. Merlos, and J. C. Laguna. 1992. Inhibition of rat liver microsomal fatty acid chain elongation by gemfibrozil in vitro. FEBS Lett. 300:89-92.
48. Schoonjans, K., B. Staels, P. Grimaldi, and J. Auwerx. 1993. Acyl-CoA synthetase mRNA expression is controlled by fibric acid derivatives, feeding and liver proliferation. Eur. J. Biochem. 216:615-622.
49. Schuhle, K., J. Gescher, U. Feil, M. Paul, M. Jahn, H. Schagger, and G. Fuchs. 2003. Benzoate-coenzyme A ligase from Thauera aromatica: an enzyme acting in anaerobic and aerobic pathways. J. Bacteriol. 185:4920-4929.
50. 2 secretion by macrophages cultured on oxidized-LDL matrices. J. Leukoc. Biol. 78:1166-1174.
51. Shah, N. S., A. Wright, G. H. Bai, L. Barrera, F. Boulahbal, N. Martin-Casabona, F. Drobniewski, C. Gilpin, M. Havelkova, R. Lepe, R. Lumb, B. Metchock, F. Portaels, M. F. Rodrigues, S. Rusch-Gerdes, A. Van Deun, V. Vincent, K. Laserson, C. Wells, and J. P. Cegielski. 2007. Worldwide emergence of extensively drug-resistant tuberculosis. Emerg. Infect. Dis. 13:380-387.
52. Smith, S. 1994. The animal fatty acid synthase: one gene, one polypeptide, seven enzymes. FASEB J. 8:1248-1259.
53. Steel, D. J., T. L. Tieman, J. H. Schwartz, and S. J. Feinmark. 1997. Identification of an 8-lipoxygenase pathway in nervous tissue of Aplysia californica. J. Biol. Chem. 272:18673-18681.
54. Tesh, M. J., and R. D. Miller. 1981. Amino acid requirements for Legionella pneumophila growth. J. Clin. Microbiol. 13:865-869.
55. Tesh, M. J., S. A. Morse, and R. D. Miller. 1983. Intermediary metabolism in Legionella pneumophila: utilization of amino acids and other compounds as energy sources. J. Bacteriol. 154:1104-1109.
56. Turnowsky, F., K. Fuchs, C. Jeschek, and G. Hogenauer. 1989. envM genes of Salmonella typhimurium and Escherichia coli. J. Bacteriol. 171:6555-6565.
57. Zahringer, U., Y. A. Knirel, B. Lindner, J. H. Helbig, A. Sonesson, R. Marre, and E. T. Rietschel. 1995. The lipopolysaccharide of Legionella pneumophila serogroup 1 (strain Philadelphia 1): chemical structure and biological significance. Prog. Clin. Biol. Res. 392:113-139.
58. Zhang, Y. M., and C. O. Rock. 2008. Membrane lipid homeostasis in bacteria. Nat. Rev. Microbiol. 6:222-233.