J Med Microbiol Track the topics, authors and articles important to you
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Erratum
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dam, T.
Right arrow Articles by Babu, C. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dam, T.
Right arrow Articles by Babu, C. R.
Agricola
Right arrow Articles by Dam, T.
Right arrow Articles by Babu, C. R.
J Med Microbiol 52 (2003), 843; DOI: 10.1099/jmm.0.05144-0
© 2003 Society for General Microbiology
ISSN 0022-2615

Plant-based siderophore: a new avenue in molecular medicine for tuberculosis

T. Dam1 and C. R. Babu2

1Dryden Hall, Room no. 216, Department of Biomedical Sciences, Oregon State University, Corvallis, OR 97331, USA 2Department of Botany, University of Delhi, Delhi, 110 007, India

Correspondence: Tapen Dam (tapen1{at}yahoo.com)


Mycobacterium tuberculosis remains a serious threat to human health, despite significant research on this organism. Study of M. tuberculosis has received increased attention because of an increase in cases of tuberculosis worldwide and a rise in incidence of drug-resistant strains.

Advances in mycobacteriology such as the completion of the M. tuberculosis genome sequence and comparative genomics using microarrays have provided impetus to the gathering of knowledge regarding the pathogenesis of this bacterium (Cole et al., 1998; Wilson et al., 1999). Understanding the molecular pathophysiology of this organism has led to the development of novel therapeutic approaches. However, peptides, proteins and nucleotides or DNA fragments, the new generation of tools against this infection, are facing problems resulting from transport, large molecular dimensions, instability at physiological pH or sensitivity to temperature. Therefore, revealing the fundamental factors regarding the host–pathogen interaction is a prerequisite for the development of new drug regimens or alternative therapies for this disease.

Mammalian host defence against the pathogen involves restricting access of the organism to iron. In vitro growth studies using standard culture media indicate that siderophore-mediated iron acquisition plays a critical role in growth and metabolism of M. tuberculosis (Olakanmi et al., 2000). Iron confers a distinct advantage on mycobacteria in their survival in the hostile host environment. In response

to iron starvation, mycobacteria produce siderophores, iron-storage protein or receptors. Currently, little is known regarding the uptake of iron by the mycobacterial siderophore and the importance of siderophores in mycobacterial pathogenesis. However, exochelins (siderophores) of M. tuberculosis are capable of removing iron from the transferrin lactoferrin and transferring it to the cell wall of mycobacteria (Gobin & Horwitz, 1996). A ten-gene cluster spanning 24 kb of the M. tuberculosis genome encoding enzymes for production of a siderophore (mycobactin) has been reported (Quadri et al., 1998).

Recently, a compound has been isolated from a root extract of the leguminous plant Tephrosia purpurea that solubilizes the compound rock iron [Fe(OH)3] and helps in plant metabolism (Aggarwal et al., 1999). This compound is also capable of inhibiting growth of M. tuberculosis H37RA under in-vitro conditions (Rajiv et al., 2001). The mechanism of action of this compound is through competition with the bacteria for iron in the environment.

We therefore propose a search for plant-based compounds that will generate new avenues to be exploited for human protection against tuberculosis. The future challenges to be met include determining the value of such plant-based compounds against invading bacteria and their effects on different components in the eukaryotic cell. This will resolve the formulation of these compounds and define an appropriate delivery system for the treatment of this infection.


   References
TOP
 References
 

  • Aggarwal, K. K., Rajiv, J. & Babu, C. R. (1999). A rock-iron-solubilizing compound from root exudates of Tephrosia purpurea. J Chem Ecol 25, 2327–2336.[CrossRef]

  • Cole, S. T., Brosch, R., Parkhill, J. & 39 other authors (1998). Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393, 537–544.[CrossRef][Medline]

  • Gobin, J. & Horwitz, M. A. (1996). Exochelins of Mycobacterium tuberculosis remove iron from human iron-binding proteins and donate iron to mycobactins in the M.tuberculosis cell wall. J Exp Med 183, 1527–1532.[Abstract/Free Full Text]

  • Olakanmi, O., Britigan, B. E. & Schlesinger, L. S. (2000). Gallium disrupts iron metabolism of mycobacteria residing within human macrophages. Infect Immun 68, 5619–5627.[Abstract/Free Full Text]

  • Quadri, L. E., Sello, J., Keating, T. A., Weinreb, P. H. & Walsh, C. T. (1998). Identification of a Mycobacterium tuberculosis gene cluster encoding the biosynthetic enzymes for assembly of the virulence-conferring siderophore mycobactin. Chem Biol 5, 631–645.[CrossRef][Medline]

  • Rajiv, J., Dam, T., Kumar, S., Bose, M., Aggarwal, K. K. & Babu, C. R. (2001). Inhibition of the in-vitro growth of Mycobacterium tuberculosis by a phytosiderophore. J Med Microbiol 50, 916–918.[Abstract/Free Full Text]

  • Wilson, M., DeRisi, J., Kristensen, H. H., Imboden, P., Rane, S., Brown, P. O. & Schoolnik, G. K. (1999). Exploring drug-induced alterations in gene expression in Mycobacterium tuberculosis by microarray hybridization. Proc Natl Acad Sci U S A 96, 12833–12838.[Abstract/Free Full Text]





    This Article
    Right arrow Full Text (PDF)
    Right arrow Erratum
    Right arrow Alert me when this article is cited
    Right arrow Alert me if a correction is posted
    Services
    Right arrow Email this article to a friend
    Right arrow Similar articles in this journal
    Right arrow Similar articles in PubMed
    Right arrow Alert me to new issues of the journal
    Right arrow Download to citation manager
    Right arrow reprints & permissions
    Citing Articles
    Right arrow Citing Articles via CrossRef
    Right arrow Citing Articles via Google Scholar
    Google Scholar
    Right arrow Articles by Dam, T.
    Right arrow Articles by Babu, C. R.
    Right arrow Search for Related Content
    PubMed
    Right arrow PubMed Citation
    Right arrow Articles by Dam, T.
    Right arrow Articles by Babu, C. R.
    Agricola
    Right arrow Articles by Dam, T.
    Right arrow Articles by Babu, C. R.

    HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
    INT J SYST EVOL MICROBIOL J MED MICROBIOL MICROBIOLOGY J GEN VIROL ALL SGM JOURNALS