Title Impact of small RNA RaoN on nitrosative-oxidative stress resistance and virulence of Salmonella enterica serovar Typhimurium
Author Sinyeon Kim1,2 and Yong Heon Lee3*
Address 1School of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea, 2Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea, 3Department of Biomedical Laboratory Science, Dongseo University, Busan 47011, Republic of Korea
Bibliography Journal of Microbiology, 58(6),499–506, 2020,
DOI 10.1007/s12275-020-0027-2
Key Words small RNA RaoN, oxidative stress, nitrosative stress, ROS, RNS, intramacrophage growth, virulence, Salmonella enterica serovar Typhimurium
Abstract RaoN is a Salmonella-specific small RNA that is encoded in the cspH-envE intergenic region on Salmonella pathogenicity island-11. We previously reported that RaoN is induced under conditions of acid and oxidative stress combined with nutrient limitation, contributing to the intramacrophage growth of Salmonella enterica serovar Typhimurium. However, the role of RaoN in nitrosative stress response and virulence has not yet been elucidated. Here we show that the raoN mutant strain has increased susceptibility to nitrosative stress by using a nitric oxide generating acidified nitrite. Extending previous research on the role of RaoN in oxidative stress resistance, we found that NADPH oxidase inhibition restores the growth of the raoN mutant in LPS-treated J774A.1 macrophages. Flow cytometry analysis further revealed that the inactivation of raoN leads to an increase in the intracellular level of reactive oxygen species (ROS) in Salmonella-infected macrophages, suggesting that RaoN is involved in the inhibition of NADPH oxidase-mediated ROS production by mechanisms not yet resolved. Moreover, we evaluated the effect of raoN mutation on the virulence in murine systemic infection and determined that the raoN mutant is less virulent than the wild-type strain following oral inoculation. In conclusion, small regulatory RNA RaoN controls nitrosativeoxidative stress resistance and is required for virulence of Salmonella in mice.