Zafirlukast inhibits complexation of lsr2 with DNA and growth of Mycobacterium tuberculosis

Lucile Pinault, Jeong Sun Han, Choong Min Kang, Jimmy Franco, Donald R. Ronning

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

The mycobacterial nucleoid-associated protein Lsr2 is a DNA-bridging protein that plays a role in condensation and structural organization of the genome and acts as a global repressor of gene transcription. Here we describe experiments demonstrating that zafirlukast inhibits the complexation between Lsr2 and DNA in vitro. Zafirlukast is shown to inhibit growth in two different species of mycobacteria tested but exhibits no growth inhibition of Escherichia coli. The Lsr2 inhibitory activity is reflected in vivo as determined by monitoring of transcription levels in Mycobacterium tuberculosis. These data suggest that zafirlukast inhibits Lsr2 function in vivo, promoting dysregulation of the expression of an array of genes typically bound by Lsr2 and hindering growth. Since zafirlukast likely operates by a mechanism distinct from current M. tuberculosis drugs and is currently used as a prophylactic treatment for asthma, it offers an intriguing lead for development of new treatments for tuberculosis.

Original languageEnglish (US)
Pages (from-to)2134-2140
Number of pages7
JournalAntimicrobial Agents and Chemotherapy
Volume57
Issue number5
DOIs
StatePublished - May 2013

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Zafirlukast inhibits complexation of lsr2 with DNA and growth of Mycobacterium tuberculosis'. Together they form a unique fingerprint.

Cite this