The heparin-binding haemagglutinin of M. tuberculosis is required for extrapulmonary dissemination

Kevin Pethe, Sylvie Alonso, Franck Biet, Giovanni Delogu, Michael J. Brennan, Camille Locht, Franco D. Menozzi

Research output: Contribution to journalArticlepeer-review

Abstract

Tuberculosis remains the world's leading cause of death due to a single infectious agent, Mycobacterium tuberculosis, with 3 million deaths and 10 million new cases per year. The infection initiates in the lungs and can then spread rapidly to other tissues. The availability of the entire M. tuberculosis genome sequence and advances in gene disruption technologies have led to the identification of several mycobacterial determinants involved in virulence. However, no virulence factor specifically involved in the extrapulmonary dissemination of M. tuberculosis has been identified to date. Here we show that the disruption of the M. tuberculosis or Mycobacterium bovis Bacille Calmette-Guérin (BCG) hbhA gene encoding the heparin-binding haemagglutinin adhesin (HBHA) markedly affects mycobacterial interactions with epithelial cells, but not with macrophage-like cells. When nasally administered to mice, the mutant strains were severely impaired in spleen colonization, but not in lung colonization. Coating wild-type mycobacteria with anti-HBHA antibodies also impaired dissemination after intranasal infection. These results provide evidence that adhesins such as HBHA are required for extrapulmonary dissemination, and that interactions with non-phagocytic cells have an important role in the pathogenesis of tuberculosis. They also suggest that antibody responses to HBHA may add to immune protection against tuberculosis.

Original languageEnglish
Pages (from-to)190-194
Number of pages5
JournalNature
Volume412
Issue number6843
DOIs
Publication statusPublished - Jul 12 2001

ASJC Scopus subject areas

  • General

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