Affiliation:
1. South Texas Center for Emerging Infectious Diseases and Department of Biology, University of Texas San Antonio, San Antonio, Texas 78249
Abstract
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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
14 articles.
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