Impact of iron loading and iron chelation on murine tuberculosis

Nacer Lounis, Caroline Maslo, Johan R. Boelaert, Pascale Bonnafous, Chantal Truffot-Pernot, Ji Baohong, Jacques Grosset

Research output: Contribution to journalArticle

Abstract

Objective: To demonstrate in a mouse model of tuberculosis that excess iron load enhances the growth of Mycobacterium tuberculosis and to assess whether or not iron chelation may abrogate the effect of iron loading on Mycobacterium tuberculosis growth in the mouse model. Methods: In the first experiment, female BALB/C mice were infected intravenously with 5.4 x 104 CFU of M. tuberculosis H37Rv per mouse. Before infection, half of them were treated for 2 weeks with 50 mg/kg polymaltose ferric hydroxide, a source of iron. In a second experiment, female BALB/C mice were infected intravenously with 9 x 104 CFU per mouse and half of them were iron loaded for 2 weeks before infection. Both iron-loaded and non-iron-loaded mice were treated with desferrioxamine (DFO), an iron chelator, or isoniazid. At each sacrifice, mice and their spleens were weighed, lung lesions were noted, and the number of M. tuberculosis CFU determined by quantitative cultures of spleen and lungs. Results: In the first experiment, the number of CFU was significantly higher in the spleen of iron-treated mice than in non-iron-loaded mice at days 14 and 28 after infection. In the second experiment, iron loading enhanced the multiplication of M. tuberculosis in the spleen but not in the lungs, DFO displayed a modest but significant effect on the multiplication of M. tuberculosis in iron-loaded mice, and isoniazid therapy was effective in both iron-loaded and non-iron-loaded mice. Conclusions: Iron loading of BALB/C mice enhanced the multiplication of M. tuberculosis in the spleens but not in the lungs. DFO exhibited significant activity against M. tuberculosis in iron-loaded mice, and isoniazid therapy was strongly bactericidal in both iron-loaded and non-iron-loaded mice.

Original languageEnglish (US)
Pages (from-to)687-692
Number of pages6
JournalClinical Microbiology and Infection
Volume5
Issue number11
DOIs
StatePublished - Nov 1999

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Keywords

  • Desferrioxamine
  • Iron
  • Isoniazid
  • Mycobacterium tuberculosis

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Lounis, N., Maslo, C., Boelaert, J. R., Bonnafous, P., Truffot-Pernot, C., Baohong, J., & Grosset, J. (1999). Impact of iron loading and iron chelation on murine tuberculosis. Clinical Microbiology and Infection, 5(11), 687-692. https://doi.org/10.1111/j.1469-0691.1999.tb00514.x