title: The protein acyltransferase Pat post-transcriptionally controls HilD to repress Salmonella invasion.
abstract: N-Lysine acylation is a post-translational modification important for both prokaryotic and eukaryotic cells to control a wide array of cellular functions. Here we demonstrate that the protein acyltransferase Pat regulates genes on Salmonella Pathogenicity Island 1 (SPI1) that are required for the invasion of the intestinal epithelium. Mutation of pat slightly increased spleen colonization by Salmonella in streptomycin-treated mice, with more of the pat mutant reaching the spleen than the wild type strain. Growth of Salmonella under specific conditions selectively induced expression of Pat, and deletion of pat increased SPI1 gene expression under the same growth conditions. In addition, over-expression of Pat repressed SPI1 expression and bacterial entry into epithelial cells. These results demonstrate that Salmonella invasion is negatively controlled by Pat. Regulation of the SPI1 central regulator HilD was essential for Pat to exert its effects. The control of HilD by Pat was through post-transcriptional mechanisms, moderately repressing hilD translation while significantly reducing HilD stability. Additionally, growth of Salmonella in the presence of histone deacetylases inhibitors reduced expression of SPI1 by affecting HilD stability, supporting the concept that altering the stability of this regulator is required for Pat to control Salmonella invasion.
authors.affiliation: Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA. ch346@cornell.edu.
authors.forename: Chien-Che
authors.initials: CC
authors.lastname: Hung
authors.affiliation: Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
authors.forename: Colleen R
authors.initials: CR
authors.lastname: Eade
authors.affiliation: Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Altier
mesh_terms: D000123:Acetyltransferases / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D044404:Genomic Islands; D051379:Mice; D008807:Mice, Inbred BALB C; D011499:Protein Processing, Post-Translational; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; C119660:HilD protein, Salmonella typhimurium; D014157:Transcription Factors; D000123:Acetyltransferases; C000619436:Pat protein, Salmonella enterica