Protein Acetylation Is Involved in Salmonella enterica Serovar Typhimurium Virulence

J Infect Dis. 2016 Jun 1;213(11):1836-45. doi: 10.1093/infdis/jiw028. Epub 2016 Jan 24.

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.

Keywords: RNA-seq; Salmonella Typhimurium; lysine acetylation; virulence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Acetyltransferases / metabolism
  • Animals
  • Bacterial Proteins / metabolism*
  • Carboxylic Ester Hydrolases / metabolism
  • Cytokines / metabolism
  • Enzyme Activation
  • Gene Deletion
  • HeLa Cells
  • Humans
  • Macrophages / microbiology
  • Mice
  • Mice, Inbred BALB C
  • Mutation
  • RAW 264.7 Cells
  • Salmonella typhimurium / enzymology
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / metabolism
  • Salmonella typhimurium / pathogenicity*
  • Transcriptome
  • Virulence

Substances

  • Bacterial Proteins
  • Cytokines
  • Spi1 protein, Salmonella
  • Acetyltransferases
  • Pat protein, Salmonella enterica
  • Carboxylic Ester Hydrolases
  • CobB protein, Salmonella enterica