title: Proteomics analysis of the causative agent of typhoid fever.
abstract: Typhoid fever is a potentially fatal disease caused by the bacterial pathogen Salmonella enterica serotype Typhi ( S. typhi). S. typhi infection is a complex process that involves numerous bacterially encoded virulence determinants, and these are thought to confer both stringent human host specificity and a high mortality rate. In the present study, we used a liquid chromatography-mass spectrometry (LC-MS)-based proteomics strategy to investigate the proteome of logarithmic, stationary phase, and low pH/low magnesium (MgM) S. typhi cultures. This represents the first large-scale comprehensive characterization of the S. typhi proteome. Our analysis identified a total of 2066 S. typhi proteins. In an effort to identify putative S. typhi-specific virulence factors, we then compared our S. typhi results to those obtained in a previously published study of the S. typhimurium proteome under similar conditions ( Adkins, J. N. et al. Mol. Cell. Proteomics 2006, 5, 1450-1461 ). Comparative proteomics analysis of S. typhi strain Ty2 and S. typhimurium strain LT2 revealed a subset of highly expressed proteins unique to S. typhi that were exclusively detected under conditions that are thought to mimic the infective state in macrophage cells. These proteins included CdtB, HlyE, and gene products of t0142, t1108, t1109, t1476, and t1602. The differential expression of T1108, T1476, and HlyE was confirmed by Western blot analysis. When our observations are taken together with the current literature, they suggest that this subset of proteins may play a role in S. typhi pathogenesis and human host specificity.
authors.affiliation: Biological Sciences Division, and Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington 99352, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Ansong
authors.forename: Hyunjin
authors.initials: H
authors.lastname: Yoon
authors.forename: Angela D
authors.initials: AD
authors.lastname: Norbeck
authors.forename: Jean K
authors.initials: JK
authors.lastname: Gustin
authors.forename: Jason E
authors.initials: JE
authors.lastname: McDermott
authors.forename: Heather M
authors.initials: HM
authors.lastname: Mottaz
authors.forename: Joanne
authors.initials: J
authors.lastname: Rue
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Adkins
authors.forename: Fred
authors.initials: F
authors.lastname: Heffron
authors.forename: Richard D
authors.initials: RD
authors.lastname: Smith
mesh_terms: D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D006801:Humans; D020543:Proteome / Q000032:analysis* / Q000096:biosynthesis / Q000737:chemistry; D040901:Proteomics; D015203:Reproducibility of Results; D012485:Salmonella typhi / Q000737:chemistry* / Q000472:pathogenicity*; D012486:Salmonella typhimurium / Q000737:chemistry / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D014435:Typhoid Fever / Q000378:metabolism / Q000382:microbiology*; D037521:Virulence Factors / Q000032:analysis* / Q000096:biosynthesis / Q000737:chemistry
chemical_list: D020543:Proteome; D037521:Virulence Factors