title: Protein Acetylation Is Involved in Salmonella enterica Serovar Typhimurium Virulence.
abstract: 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 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 mutants in S. Typhimurium and found that pat is critical for bacterial intestinal colonization and systemic infection. Next, to understand the underlying mechanism, genome-wide transcriptome was analyzed. RNA sequencing data showed that the expression of Salmonella pathogenicity island 1 (SPI-1) is partially dependent on pat In addition, we found that HilD, a key transcriptional regulator of SPI-1, is a substrate of Pat. The acetylation of HilD by Pat maintained HilD stability and was essential for the transcriptional activation of HilA. Taken together, these results suggest that a protein acetylation system regulates SPI-1 expression by controlling HilD in a posttranslational manner to mediate S. Typhimurium virulence.
authors.affiliation: Laboratory of Bacterial Pathogenesis, Department of Microbiology and Immunology, Institutes of Medical Sciences.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sang
authors.affiliation: Laboratory of Bacterial Pathogenesis, Department of Microbiology and Immunology, Institutes of Medical Sciences.
authors.forename: Jie
authors.initials: J
authors.lastname: Ren
authors.affiliation: Laboratory of Bacterial Pathogenesis, Department of Microbiology and Immunology, Institutes of Medical Sciences.
authors.forename: Jinjing
authors.initials: J
authors.lastname: Ni
authors.affiliation: Laboratory of Bacterial Pathogenesis, Department of Microbiology and Immunology, Institutes of Medical Sciences.
authors.forename: Jing
authors.initials: J
authors.lastname: Tao
authors.affiliation: Department of Infectious Diseases, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine.
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.affiliation: Laboratory of Bacterial Pathogenesis, Department of Microbiology and Immunology, Institutes of Medical Sciences Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, China.
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Yao
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004789:Enzyme Activation; D017353:Gene Deletion; D006367:HeLa Cells; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D000067996:RAW 264.7 Cells; D012486:Salmonella typhimurium / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D059467:Transcriptome; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; C419942:Spi1 protein, Salmonella; D000123:Acetyltransferases; C000619436:Pat protein, Salmonella enterica; D002265:Carboxylic Ester Hydrolases; C000619437:CobB protein, Salmonella enterica
keywords: RNA-seq; Salmonella Typhimurium; lysine acetylation; virulence