Gallium disrupts iron metabolism of mycobacteria residing within human macrophages

O. Olakanmi, B. E. Britigan, L. S. Schlesinger

Research output: Contribution to journalArticle

155 Citations (Scopus)

Abstract

Mycobacterium tuberculosis and M. avium complex (MAC) enter and multiply within monocytes and macrophages in phagosomes. In vitro growth studies using standard culture media indicate that siderophoremediated iron (Fe) acquisition plays a critical role in the growth and metabolism of both M. tuberculosis and MAC. However, the applicability of such studies to conditions within the macrophage phagosome is unclear, due in part to the absence of experimental means to inhibit such a process. Based on the ability of gallium (Ga3+) to concentrate within mononuclear phagocytes and on evidence that Ga disrupts cellular Fe-dependent metabolic pathways by substituting for Fe3+ and failing to undergo redox cycling, we hypothesized that Ga could disrupt Fe acquisition and Fe-dependent metabolic pathways of mycobacteria. We find that Ga(NO3)3 and Ga-transferrin produce an Fe-reversible concentration-dependent growth inhibition of M. tuberculosis strains and MAC grown extracellularly and within human macrophages. Ga is bactericidal for M. tuberculosis growing extracellularly and within macrophages. Finally, we provide evidence that exogenously added Fe is acquired by intraphagosomal M. tuberculosis and that Ga inhibits this Fe acquisition. Thus, Ga(NO3)3 disruption of mycobacterial Fe metabolism may serve as an experimental means to study the mechanism of Fe acquisition by intracellular mycobacteria and the role of Fe in intracellular survival. Furthermore, given the inability of biological systems to discriminate between Ga and Fe, this approach could have broad applicability to the study of Fe metabolism of other intracellular pathogens.

Original languageEnglish (US)
Pages (from-to)5619-5627
Number of pages9
JournalInfection and immunity
Volume68
Issue number10
DOIs
StatePublished - Jan 1 2000

Fingerprint

Gallium
Mycobacterium
Mycobacterium tuberculosis
Iron
Macrophages
Phagosomes
Metabolic Networks and Pathways
Growth
Transferrin
Phagocytes
Oxidation-Reduction
Culture Media
Monocytes
Survival

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Gallium disrupts iron metabolism of mycobacteria residing within human macrophages. / Olakanmi, O.; Britigan, B. E.; Schlesinger, L. S.

In: Infection and immunity, Vol. 68, No. 10, 01.01.2000, p. 5619-5627.

Research output: Contribution to journalArticle

Olakanmi, O. ; Britigan, B. E. ; Schlesinger, L. S. / Gallium disrupts iron metabolism of mycobacteria residing within human macrophages. In: Infection and immunity. 2000 ; Vol. 68, No. 10. pp. 5619-5627.
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