Compensatory role of KatG in defending H2O2 stress in msr deletion strain of Salmonella Typhimurium

Abstract

KatG and Msrs are important enzymes associated with ROS homeostasis and bacterial survival under oxidative stress. Consistent to this notion, mutant strains in these enzymes showed hypersensitivity to oxidants and accumulates elevated levels of ROS. In current study we observed that a pan msr deletion ({Delta}5msr mutant) strain of S. Typhimurium accumulates significantly higher levels of ROS. However, unexpectedly, as compared to S. Typhimurium, the {Delta}5msr mutant strain exhibits more than 2000 folds resistance to H2O2. Transcriptional and mass spectrometry analyses reveal the upregulation of KatG in {Delta}5msr mutant strain. Further, {Delta}5msr mutant strain exhibits [~]6 folds higher KatG activity. Supplementation of {Delta}5msr mutant culture with reduced glutathione resulted in ROS neutralization, decreased KatG activity and abrogation of H2O2 resistance. However, {Delta}5msr mutant strain showed negligible KatE and KatN activities. The findings of current study suggest that the Salmonella have evolved the mechanism to upregulate one antioxidant gene in absence of others to mitigate oxidative stress.