Protein Acetylation Is Involved In Salmonella Enterica Serovar Typhimurium Virulence

Salmonella causes a range of diseases in different hosts,including enterocolitis and systemic infection.Lysine acetylation regulates many eukaryotic cellular processes,but its function in bacteria is largely unexplored.The acetyltransferase Pat and nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylase CobB are involved in the reversible protein acetylation in Salmonella Typhimurium.Here,we used cell and animal models to evaluate the virulence of pat and cobB deletion mutantsin S.Typhimurium,and found that pat has a contribution for bacterial intestinal colonization,systemic infection.Next,to understand the underlying mechanism,genome-wide transcriptome was analyzed.RNA-seq data showed the expression of Salmonella pathogenicity islands 1(SPI-1)is partially dependent on pat.In addition,we found that HilD is a substrate of Pat which occupies the apex of the regulatory cascade within SPI-1.The acetylation of HilD by Pat maintained HilD stability and was essential for the transcriptional activation of HilA.Further,mass spectrometry and anti-HilD K297Ac specific polyclonal antibody were used to identify the acetylation site was K297,and its acetylation would increase the stability of HilD.Taken together,these results suggest that protein acetylation system regulates SPI-1 expression by controlling HilD stability in a post-translational manner to mediate S.Typhimurium virulence.