103 : Virulent Francisella tularensis do not induce arginase as a mechanism of virulence

Abstract

Induction of arginase by intracellular pathogens has been shown to contribute to the ability of bacteria to replicate in the host cell and is considered an important aspect of virulence. However, it is not known if induction of arginase plays a significant role in pathogenesis of the intracellular bacterium Francisella tularensis . We sought to determine if F. tularensis infection resulted in arginase induction, and if this was an important mechanism of virulence for the bacteria. We found that arginase was not induced following F. tularensis subsp. tularensis (SchuS4) or subsp. holarctica (Live Vaccine Strain [LVS]) infection in an in vitro gentamicin protection assay: IL-4 treated cells induced a statistically significant upregulation of arginase, as expected, while F. tularensis infected cells did not. In addition, we infected C57Bl/6 mice intranasally with F. tularensis and determined if arginase was induced in the lungs or bronchoalveolar lavage fluid. We found that arginase was not significantly induced following infection with either strain as compared to uninfected control mice. Finally, we infected Arg1 −/− cells with either SchuS4 or LVS and determined if there was a difference in replication compared to wild-type cells. We found that there was not a statistically significant difference in survival or replication of either strain of bacteria between Arg1 −/− and wild-type cells. Therefore, we conclude that for F. tularensis , arginase induction is not important for virulence.