Isoniazid resistance without a loss of fitness in Mycobacterium tuberculosis

Jong Hee Lee, Nicole C. Ammerman, Scott Nolan, Deborah E. Geiman, Shichun Lun, Haidan Guo, William R. Bishai

Research output: Contribution to journalArticle

Abstract

The emergence of multi- and extensively drug-resistant tuberculosis (MDR-TB and XDR-TB, respectively) has intensified the critical public health implications of this global disease. The fitness of Mycobacterium tuberculosis (M.tb.) strains exhibiting MDR and XDR phenotypes is of fundamental importance in predicting whether the MDR-/XDR-TB epidemic will be sustained across the human population. Here we describe a potential mechanism of M.tb. resistance to the TB drug isoniazid (INH) conferred by loss of a sigma factor, SigI. We demonstrate that the gain of INH resistance in the M.tb. ΔsigI mutant might not diminish the organism's fitness for causing disease. These findings have significant implications when considering the ability of drug-resistant M.tb. strains to initiate untreatable TB epidemics, as it is possible that loss or alteration of SigI function could have a role in the generation of MDR and XDR M.tb. strains of suitable fitness to spread in a community setting.

Original languageEnglish (US)
Article number1724
JournalNature communications
Volume3
DOIs
StatePublished - Apr 4 2012

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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