1887

Abstract

under stress stores triacylglycerol (TG). There are 15 genes in that belong to a novel family of TG synthase genes (), but it is not known which of them is responsible for this accumulation of TG. In this paper, it is reported that H37Rv accumulated TG under acidic, static or hypoxic growth conditions, or upon treatment with NO, whereas TG accumulation was drastically reduced in the (Rv3130c) disrupted mutant. Complementation with restored this TG accumulation. C was a major fatty acid in this TG, indicating that the TGS1 gene product uses C fatty acid, which is known to be produced by the mycobacterial fatty acid synthase. TGS1 expressed in preferred C-CoA for TG synthesis. If TG storage is needed for the long-term survival of s under dormant conditions, the product could be a suitable target for antilatency drugs.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.28993-0
2006-09-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/micro/152/9/2717.html?itemId=/content/journal/micro/10.1099/mic.0.28993-0&mimeType=html&fmt=ahah

References

  1. Bardarov S, Sambandamurthy V, Larsen M, Tufariello J, Chan J, Hatfull G, Bardarov S. Jr, Pavelka M. S. Jr, Jacobs W. R. Jr 2002; Specialized transduction: an efficient method for generating marked and unmarked targeted gene disruptions in Mycobacterium tuberculosis , M.bovis BCG and M. smegmatis . Microbiology 148:3007–3017
    [Google Scholar]
  2. Betts J. C, Lukey P. T, Robb L. C, McAdam R. A, Duncan K. 2002; Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling. Mol Microbiol 43:717–731 [CrossRef]
    [Google Scholar]
  3. Brindley D. N, Matsumura S, Bloch K. 1969; Mycobacterium phlei fatty acid synthase – a bacterial multienzyme complex. Nature 224:666–669 [CrossRef]
    [Google Scholar]
  4. Chan E. D, Chan J, Schluger N. W. 2001; What is the role of nitric oxide in murine and human host defense against tuberculosis? Current knowledge. J Respir Cell Mol Biol 25:606–612 [CrossRef]
    [Google Scholar]
  5. Cosma C. L, Sherman D. R, Ramakrishnan L. 2003; The secret lives of the pathogenic mycobacteria. Annu Rev Microbiol 57:641–676 [CrossRef]
    [Google Scholar]
  6. Daniel J, Deb C, Dubey V. S, Sirakova T. D, Abomoelak B, Morbidoni H. R, Kolattukudy P. E. 2004; Induction of a novel class of diacylglycerol acyltransferases and triacylglycerol accumulation in Mycobacterium tuberculosis as it goes into a dormancy-like state in culture. J Bacteriol 186:5017–5030 [CrossRef]
    [Google Scholar]
  7. Derbyshire K. M, Bardarov S. 2000; DNA transfer in mycobacteria: conjugation and transduction. In Molecular Genetics of Mycobacteria pp  93–107 Edited by Hatfull G. F., Jacobs W. R. Jr Washington, DC: American Society for Microbiology;
    [Google Scholar]
  8. Fisher M. A, Plikaytis B. B, Shinnick T. M. 2002; Microarray analysis of the Mycobacterium tuberculosis transcriptional response to the acidic conditions found in phagosomes. J Bacteriol 184:4025–4032 [CrossRef]
    [Google Scholar]
  9. Florczyk M. A, McCue L. A, Purkayastha A, Currenti E, Wolin M. J, McDonough K. A. 2003; A family of acr acr-coregulated Mycobacterium tuberculosis genes shares a common DNA motif and requires Rv3133c (dosR or devR) for expression. Infect Immun 71:5332–5343 [CrossRef]
    [Google Scholar]
  10. Garton N. J, Christensen H, Minnikin D. E, Adegbola R. A, Barer M. R. 2002; Intracellular lipophilic inclusions of mycobacteria in vitro in vitro and in sputum. Microbiology 148:2951–2958
    [Google Scholar]
  11. Gomez J. E, McKinney J. D. 2004; M. tuberculosis persistence, latency, and drug tolerance. Tuberculosis 84:29–44 [CrossRef]
    [Google Scholar]
  12. Jackson S. K, Stark J. M, Taylor S, Harwood J. L. 1989; Changes in phospholipids fatty acid composition and triacylglycerol content in mouse tissues after infection with bacilli Calmette–Guerin. Br J Exp Pathol 70:435–441
    [Google Scholar]
  13. Kalscheuer R, Steinbuchel A. 2003; A novel bifunctional wax ester synthase/acyl-CoA: diacylglycerol acyltransferase mediates wax ester and triacylglycerol biosynthesis in Acinetobacter calcoaceticus ADP1. J Biol Chem 278:8075–8082 [CrossRef]
    [Google Scholar]
  14. Kikuchi S, Rainwater D. L, Kolattukudy P. E. 1992; Purification and characterization of an unusually large fatty acid synthase from Mycobacterium tuberculosis var. bovis BCG. Arch Biochem Biophys 295:318–326 [CrossRef]
    [Google Scholar]
  15. LeDantec C, Winter N, Gicquel B, Vincent V, Picardeau M. 1991; Genomic sequence and transcriptional analysis of a 23-kilobase mycobacterial linear plasmid: evidence for horizontal transfer and identification of plasmid maintence systems. J Bacteriology 183:2157–2164
    [Google Scholar]
  16. Munoz-Elias E. J, McKinney J. D. 2005; Mycobacterium tuberculosis isocitrate lyases 1 and 2 are jointly required for in vivo growth and virulence. Nat Med 11:638–644 [CrossRef]
    [Google Scholar]
  17. Nathan C. 2002; Inducible nitric oxide synthase in the tuberculous human lung. Am J Respir Crit Care Med 166:130–131 [CrossRef]
    [Google Scholar]
  18. Ohno H, Zhu G, Mohan V. P, Chu D, Kohno S, Chan J, Jacobs W. R. Jr 2003; The effects of reactive nitrogen intermediates on gene expression in Mycobacterium tuberculosis . Cell Microbiol 5:637–648 [CrossRef]
    [Google Scholar]
  19. Park H. D, Guinn K. M, Harrell M. I, Liao R, Voskuil M. I, Tompa M, Schoolnik G. K, Sherman D. R. 2003; Rv3133c/dosR is a transcription factor that mediates the hypoxic response of Mycobacterium tuberculosis . Mol Microbiol 48:833–843 [CrossRef]
    [Google Scholar]
  20. Russell D. G. 2003; Phagosomes, fatty acids and tuberculosis. Nat Cell Biol 5:776–778 [CrossRef]
    [Google Scholar]
  21. Sassetti C. M, Rubin E. J. 2003; Genetic requirements for mycobacterial survival during infection. Proc Natl Acad Sci U S A 100:12989–12994 [CrossRef]
    [Google Scholar]
  22. Saviola B, Woolwine S. C, Bishai W. R. 2003; Isolation of acid-inducible genes of Mycobacterium tuberculosis with the use of recombinase-based in vivo expression technology. Infect Immun 71:1379–1388 [CrossRef]
    [Google Scholar]
  23. Schnappinger D, Ehrt S, Voskuil M. I. 8 other authors 2003; Transcriptional adaptation of Mycobacterium tuberculosis within macrophages: insights into the phagosomal environment. J Exp Med 198:693–704 [CrossRef]
    [Google Scholar]
  24. Segal W, Bloch H. 1956; Biochemical differentiation of Mycobacterium tuberculosis grown in vivo and in vitro . J Bacteriol 72:132–141
    [Google Scholar]
  25. Sirakova T. D, Thirumala A. K, Dubey V. S, Sprecher H, Kolattukudy P. E. 2001; The Mycobacterium tuberculosis pks 2 gene encodes the synthase for the hepta- and octamethyl-branched fatty acids required for sulfolipid synthesis. J Biol Chem 276:16833–16839 [CrossRef]
    [Google Scholar]
  26. Voskuil M. I, Schnappinger D, Visconti K. C, Harrell M. I, Dolganov G. M, Sherman D. R, Schoolnik G. K. 2003; Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program. J Exp Med 198:705–713 [CrossRef]
    [Google Scholar]
  27. Wayne L. G, Sohaskey C. D. 2001; Nonreplicating persistence of Mycobacterium tuberculosis . Annu Rev Microbiol 55:139–163 [CrossRef]
    [Google Scholar]
  28. World Health Organization 2005; Global tuberculosis control. http://www.who.int/tb/publications/2005/en/index.html
    [Google Scholar]
  29. Zahrt T. C. 2003; Molecular mechanisms regulating persistent Mycobacterium tuberculosis infection. Microbes Infect 5:159–167 [CrossRef]
    [Google Scholar]
  30. Zhang Y. 2004; Persistent and dormant bacilii and latent tuberculosis. Front Biosci 9:1136–1156 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.28993-0
Loading
/content/journal/micro/10.1099/mic.0.28993-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error