title: Formate acts as a diffusible signal to induce Salmonella invasion.
abstract: To infect an animal host, Salmonella enterica serovar Typhimurium must penetrate the intestinal epithelial barrier. This process of invasion requires a type III secretion system encoded within Salmonella pathogenicity island I (SPI1). We found that a mutant with deletions of the acetate kinase and phosphotransacetylase genes (ackA-pta) was deficient in invasion and SPI1 expression but that invasion gene expression was completely restored by supplying medium conditioned by growth of the wild-type strain, suggesting that a signal produced by the wild type, but not by the ackA-pta mutant, was required for invasion. This mutant also excreted 68-fold-less formate into the culture medium, and the addition of sodium formate to cultures restored both the expression of SPI1 and the invasion of cultured epithelial cells by the mutant. The effect of formate was pH dependent, requiring a pH below neutrality, and studies in mice showed that the distal ileum, the preferred site of Salmonella invasion in this species, had the appropriate formate concentration and pH to elicit invasion, while the cecum contained no detectable formate. Furthermore, we found that formate affected the major regulators of SPI1, hilA and hilD, but that the primary routes of formate metabolism played no role in its activity as a signal.
authors.affiliation: Department of Population Medicine and Diagnostic Sciences, Upper Tower Road, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Huang
authors.forename: Mitsu
authors.initials: M
authors.lastname: Suyemoto
authors.forename: Cherilyn D
authors.initials: CD
authors.lastname: Garner
authors.forename: Kellie M
authors.initials: KM
authors.lastname: Cicconi
authors.forename: Craig
authors.initials: C
authors.lastname: Altier
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004847:Epithelial Cells / Q000382:microbiology; D005260:Female; D005561:Formates / Q000378:metabolism / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D044404:Genomic Islands / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D011522:Protons; D019289:Pyruvic Acid / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D017077:Culture Media, Conditioned; D005561:Formates; D011522:Protons; C094578:Salmonella invasion protein C; C030544:formic acid; D019289:Pyruvic Acid