Abstract
Salmonella Typhimurium (STM) is a facultative anaerobe of zoonotic
importance and one of the causative agents of non-typhoidal
salmonellosis (NTS). During infection, STM must adapt to the changes in
oxygen concentration encountered in the crucial niches of host like gut
lumen and intramacrophage environments. But being a
chemo-organoheterotroph, STM is capable of obtaining its energy from
organic sources via redox reactions. NarL, a transcription factor and
the response regulator of the two-component regulatory system NarX/L,
gets activated under nitrate rich anaerobic condition. Upon activation,
it upregulates the nitrate reduction during anaerobic respiration.
However, in this study, we observed a significant attenuation of
virulence in the narL-knockout strain of STM, while the respective
morphotypes got rescued upon genetic complementation. Along with
motility and biofilm forming ability, the mutant strain displayed
reduced intracellular replication in either intestinal epithelial cells
or monocyte-derived macrophages of poultry origin. Further, in vivo
competitive assay in the murine model showed that wild type STM
significantly outcompeted its isogenic narL null mutant.