Genetic requirements for the survival of tubercle bacilli in primates

Noton K. Dutta, Smriti Mehra, Peter J. Didier, Chad J. Roy, Lara A. Doyle, Xavier Alvarez, Marion Ratterree, Nicholas A. Be, Gyanu Lamichhane, Sanjay K. Jain, Michelle R. Lacey, Andrew A. Lackner, Deepak Kaushal

Research output: Contribution to journalArticle

Abstract

Background. Tuberculosis (TB) leads to the death of 1.7 million people annually. The failure of the bacille Calmette-Guérin vaccine, synergy between AIDS and TB, and the emergence of drug resistance have worsened this situation. It is imperative to delineate the mechanisms employed by Mycobacterium tuberculosis to successfully infect and persist in mammalian lungs. Methods. Nonhuman primates (NHPs) are arguably the best animal system to model critical aspects of human TB. We studied genes essential for growth and survival of M. tuberculosis in the lungs of NHPs experimentally exposed to aerosols of an M. tuberculosis transposon mutant library. Results. Mutants in 108 M. tuberculosis genes (33.13% of all genes tested) were attenuated for in vivo growth. Comparable studies have reported the attenuation of only ∼6% of mutants in mice. The M. tuberculosis mutants attenuated for in vivo survival in primates were involved in the transport of various biomolecules, including lipid virulence factors; biosynthesis of cell-wall arabinan and peptidoglycan; DNA repair; sterol metabolism; and mammalian cell entry. Conclusions. Our study highlights the various virulence mechanisms employed by M. tuberculosis to overcome the hostile environment encountered during infection of primates. Prophylactic approaches aimed against bacterial factors that respond to such in vivo stressors have the potential to prevent infection at an early stage, thus likely reducing the extent of transmission of M. tuberculosis.

Original languageEnglish (US)
Pages (from-to)1743-1752
Number of pages10
JournalJournal of Infectious Diseases
Volume201
Issue number11
DOIs
StatePublished - Jun 1 2010

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Dutta, N. K., Mehra, S., Didier, P. J., Roy, C. J., Doyle, L. A., Alvarez, X., Ratterree, M., Be, N. A., Lamichhane, G., Jain, S. K., Lacey, M. R., Lackner, A. A., & Kaushal, D. (2010). Genetic requirements for the survival of tubercle bacilli in primates. Journal of Infectious Diseases, 201(11), 1743-1752. https://doi.org/10.1086/652497