Comparative proteomic analysis of the PhoP regulon in Salmonella enterica serovar Typhi versus Typhimurium

• Published in: PloS one Vol. 4; no. 9; p. e6994
• Main Authors: Charles, Richelle C, Harris, Jason B, Chase, Michael R, Lebrun, Lauren M, Sheikh, Alaullah, LaRocque, Regina C, Logvinenko, Tanya, Rollins, Sean M, Tarique, Abdullah, Hohmann, Elizabeth L, Rosenberg, Ian, Krastins, Bryan, Sarracino, David A, Qadri, Firdausi, Calderwood, Stephen B, Ryan, Edward T
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.09.2009; Public Library of Science (PLoS)
• Subjects: Animals; Bacteria; Bacterial Proteins - metabolism; Bacterial Vaccines - metabolism; Cell cycle; Chromatography; Chromosomes; Comparative analysis; Cytolethal distending toxin; Deoxyribonucleic acid; Distension; DNA; DNA damage; E coli; Escherichia coli; Fever; Gastroenteritis; Gene expression; Gene Expression Regulation, Bacterial; Genetics and Genomics/Gene Expression; Genomes; Genomics; Health aspects; High performance liquid chromatography; Homology; Hospitals; Humans; Illnesses; Immunology; Infectious Diseases; Infectious Diseases/Bacterial Infections; Infectious Diseases/Gastrointestinal Infections; Infectious Diseases/Neglected Tropical Diseases; Intracellular; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Medical research; Medical schools; Medicine; Mice; Microbiology; Microbiology/Cellular Microbiology and Pathogenesis; Microbiology/Immunity to Infections; Models, Biological; Mutants; Mutation; Oxidative stress; Peptides; Peptides - chemistry; Pore formation; Proteins; Proteomics - methods; Public health; Regulation; RNA; Salmonella; Salmonella food poisoning; Salmonella typhi - metabolism; Salmonella Typhimurium; Salmonella typhimurium - metabolism; Species Specificity; Strains (organisms); Typhoid; Typhoid fever; Virulence; Virulence (Microbiology); Virulence - genetics; Water-borne diseases; Waterborne diseases; United States > US; Bangladesh; Massachusetts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0006994

S. Typhi, a human-restricted Salmonella enterica serovar, causes a systemic intracellular infection in humans (typhoid fever). In comparison, S. Typhimurium causes gastroenteritis in humans, but causes a systemic typhoidal illness in mice. The PhoP regulon is a well studied two component (PhoP/Q) coordinately regulated network of genes whose expression is required for intracellular survival of S. enterica. Using high performance liquid chromatography mass spectrometry (HPLC-MS/MS), we examined the protein expression profiles of three sequenced S. enterica strains: S. Typhimurium LT2, S. Typhi CT18, and S. Typhi Ty2 in PhoP-inducing and non-inducing conditions in vitro and compared these results to profiles of phoP(-)/Q(-) mutants derived from S. Typhimurium LT2 and S. Typhi Ty2. Our analysis identified 53 proteins in S. Typhimurium LT2 and 56 proteins in S. Typhi that were regulated in a PhoP-dependent manner. As expected, many proteins identified in S. Typhi demonstrated concordant differential expression with a homologous protein in S. Typhimurium. However, three proteins (HlyE, STY1499, and CdtB) had no homolog in S. Typhimurium. HlyE is a pore-forming toxin. STY1499 encodes a stably expressed protein of unknown function transcribed in the same operon as HlyE. CdtB is a cytolethal distending toxin associated with DNA damage, cell cycle arrest, and cellular distension. Gene expression studies confirmed up-regulation of mRNA of HlyE, STY1499, and CdtB in S. Typhi in PhoP-inducing conditions. This study is the first protein expression study of the PhoP virulence associated regulon using strains of Salmonella mutant in PhoP, has identified three Typhi-unique proteins (CdtB, HlyE and STY1499) that are not present in the genome of the wide host-range Typhimurium, and includes the first protein expression profiling of a live attenuated bacterial vaccine studied in humans (Ty800).