The Rcs phosphorelay system is specific to enteric pathogens/commensals and activates ydeI, a gene important for persistent Salmonella infection of mice.
Bacteria utilize phosphorelay systems to respond to environmental or intracellular stimuli. Salmonella enterica encodes a four-step phosphorelay system that involves two sensor kinase proteins, RcsC and RcsD, and a response regulator, RcsB. The physiological stimulus for Rcs phosphorelay activation is unknown; however, Rcs-regulated genes can be induced in vitro by osmotic shock, low temperature and antimicrobial peptide exposure. In this report we investigate the role of the Rcs pathway using phylogenetic analysis and experimental techniques. Phylogenetic analysis determined that full-length RcsC- and RcsD-like proteins are generally restricted to Enterobacteriaceae species that have an enteric pathogenic or commensal relationship with the host. Experimental data show that RcsD and RcsB, in addition to RcsC, are important for systemic infection in mice and polymyxin B resistance in vitro. To identify Rcs-regulated genes that confer these phenotypes, we took advantage of our observation that RcsA, a transcription factor and binding partner of RcsB, is not required for polymyxin B resistance or survival in mice. S. enterica serovar Typhimurium oligonucleotide microarrays were used to identify 18 loci that are activated by RcsC, RcsD and RcsB but not RcsA. Five of the 18 loci encode genes that contribute to polymyxin B resistance. One of these genes, ydeI, was shown by quantitative real-time PCR to be regulated by the Rcs pathway independently of RcsA. Additionally, the stationary-phase sigma factor, RpoS (sigmaS), regulates ydeI transcription. In vivo infections show that ydeI mutants are out-competed by wild type 10- to 100-fold after oral inoculation, but are only modestly attenuated after intraperitoneal inoculation. These data indicate that ydeI is an Rcs-activated gene that plays an important role in persistent infection of mice, possibly by increasing bacterial resistance to antimicrobial peptides.
Erickson
Kimberly D
KD
Department of Molecular, Cellular and Developmental Biology, University of Colorado at Boulder, Boulder, CO 80309, USA.
Detweiler
Corrella S
CS
D000249:Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001426:Bacterial Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D024881:Drug Resistance, Bacterial / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism; D010770:Phosphotransferases / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D011112:Polymyxin B / Q000494:pharmacology; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D012480:Salmonella Infections / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity*; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D009097:Multienzyme Complexes; D012808:Sigma Factor; D014157:Transcription Factors; C495282:YojN protein, Salmonella typhimurium; C069567:sigma factor KatF protein, Bacteria; C074889:RcsB protein, Bacteria; D000249:Adenosine Monophosphate; D010770:Phosphotransferases; D011494:Protein Kinases; C434271:rcsD protein, E coli; D010749:Phosphoprotein Phosphatases; D011112:Polymyxin B