The Role Of Methylation In Regulateing PhoP Activity And Salmonella Enterica Serovar Typhimurium Virulence

The PhoP-PhoQ two-component regulation system of Salmonella enterica serovar Typhimurium(S.Typhimurium)is involved in response with various environmental stresses and is important for bacterial virulence.Previous study showed that the acetylation inhibits PhoP activity and leads to reduced virulence of Salmonella.Here,we demonstrated that the conserved arginine residue 112(R112)of PhoP could be specifically methylated by CheR.The methylation level of PhoP R112 was significantly decreased in response to low magnesium condition,acid stress or phagocytosis of macrophages.Besides,we found that R112 is located in α4-β5-α5 of the receiver domain which is crucial for PhoP dimerization.R112 mutation such as mutant to A,the activity of PhoP will be decreased,due to weaker dimer-formation and DNA-binding activity.In addition,R112 A in S.Typhimurium dramatically attenuated intestinal inflammation and systemic infection in mouse model,suggesting that R112 is essential for PhoP to regulate Salmonella virulence.Overexpression of CheR increased methylation of R112 and decreased dimer-formation and DNA-binding of PhoP,but increase the stability of PhoP.These findings indicated that arginine methylation of PhoP involved in its dimer-formation and DNA-binding as a novel regulatory mechanism for Salmonella virulence.