The multifunctional histone-like protein Lsr2 protects mycobacteria against reactive oxygen intermediates

R. Colangeli, A. Haq, V. L. Arcus, E. Summers, R. S. Magliozzo, A. McBride, A. K. Mitra, M. Radjainia, A. Khajo, W. R. Jacobs, P. Salgame, D. Alland

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Mycobacterium tuberculosis has evolved a number of strategies to survive within the hostile environment of host phagocytes. Reactive nitrogen and oxygen intermediates (RNI and ROI) are among the most effective antimycobacterial molecules generated by the host during infection. Lsr2 is a M. tuberculosis protein with histone- like features, including the ability to regulate a variety of tran- scriptional responses in mycobacteria. Here we demonstrate that Lsr2 protects mycobacteria against ROI in vitro and during macro- phage infection. Furthermore, using macrophages derived from NOS -/- and Phox -/- mice, we demonstrate that Lsr2 is important in protecting against ROI but not RNI. The protection provided by Lsr2 protein is not the result of its ability to either bind iron or scavenge hydroxyl radicals. Instead, electron microscopy and DNA- binding studies suggest that Lsr2 shields DNA from reactive intermediates by binding bacterial DNA and physically protecting it. Thus, Lsr2 appears to be a unique protein with both histone-like properties and protective features that may be central to M. tuberculosis pathogenesis. In addition, evidence indicates that lsr2 is an essential gene in M. tuberculosis. Because of its essentiality, Lsr2 may represent an excellent candidate as a drug target.

Original languageEnglish (US)
Pages (from-to)4414-4418
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number11
DOIs
StatePublished - Mar 17 2009

Keywords

  • DNA
  • DPS
  • Mycobacterium tuberculosis
  • ROl

ASJC Scopus subject areas

  • General

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