Tryptophan prototrophy contributes to Francisella tularensis evasion of gamma interferon-mediated host defense

Ping Chu, Annette R. Rodriguez, Bernard P. Arulanandam, Karl E. Klose

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Francisella tularensis is able to survive and replicate within host macrophages, a trait that is associated with the high virulence of this bacterium. The trpAB genes encode the enzymes required for the final two steps in tryptophan biosynthesis, with TrpB being responsible for the conversion of indole to tryptophan. Consistent with this function, an F. tularensis subsp. novicida trpB mutant is unable to grow in defined medium in the absence of tryptophan. The trpB mutant is also attenuated for virulence in a mouse pulmonary model of tularemia. However, the trpB mutant remains virulent in gamma interferon receptor-deficient (IFN-γR-/-) mice, demonstrating that IFN-γ-mediated signaling contributes to clearance of the trpB mutant. IFN-γ limits intracellular survival of the trpB mutant within bone marrow-derived macrophages from wild-type but not IFN-γR-/- mice. An F. tularensis subsp. tularensis trpB mutant is also attenuated for virulence in mice and survival within IFN-γ-treated macrophages, indicating that tryptophan prototrophy is also important in a human-virulent F. tularensis subspecies. These results demonstrate that trpB contributes to F. tularensis virulence by enabling intracellular growth under IFN-γ-mediated tryptophan limitation.

Original languageEnglish (US)
Pages (from-to)2356-2361
Number of pages6
JournalInfection and immunity
Volume79
Issue number6
DOIs
StatePublished - Jun 2011

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Tryptophan prototrophy contributes to Francisella tularensis evasion of gamma interferon-mediated host defense'. Together they form a unique fingerprint.

Cite this