title: The Shigella dysenteriae serotype 1 proteome, profiled in the host intestinal environment, reveals major metabolic modifications and increased expression of invasive proteins.
abstract: Shigella dysenteriae serotype 1 (SD1) causes the most severe form of epidemic bacillary dysentery. We present the first comprehensive proteome analysis of this pathogen, profiling proteins from bacteria cultured in vitro and bacterial isolates from the large bowel of infected gnotobiotic piglets (in vivo). Overall, 1061 distinct gene products were identified. Differential display analysis revealed that SD1 cells switched to an anaerobic energy metabolism in vivo. High in vivo abundances of amino acid decarboxylases (GadB and AdiA) which enhance pH homeostasis in the cytoplasm and protein disaggregation chaperones (HdeA, HdeB and ClpB) were indicative of a coordinated bacterial survival response to acid stress. Several type III secretion system effectors were increased in abundance in vivo, including OspF, IpaC and IpaD. These proteins are implicated in invasion of colonocytes and subversion of the host immune response in S. flexneri. These observations likely reflect an adaptive response of SD1 to the hostile host environment. Seven proteins, among them the type III secretion system effectors OspC2 and IpaB, were detected as antigens in Western blots using piglet antisera. The outer membrane protein OmpA, the heat shock protein HtpG and OspC2 represent novel SD1 subunit vaccine candidates and drug targets.
authors.affiliation: Pathogen Functional Genomics Resource Center, J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, MD 20850, USA. rpieper@jcvi.org
authors.forename: Rembert
authors.initials: R
authors.lastname: Pieper
authors.forename: Quanshun
authors.initials: Q
authors.lastname: Zhang
authors.forename: Prashanth P
authors.initials: PP
authors.lastname: Parmar
authors.forename: Shih-Ting
authors.initials: ST
authors.lastname: Huang
authors.forename: David J
authors.initials: DJ
authors.lastname: Clark
authors.forename: Hamid
authors.initials: H
authors.lastname: Alami
authors.forename: Arthur
authors.initials: A
authors.lastname: Donohue-Rolfe
authors.forename: Robert D
authors.initials: RD
authors.lastname: Fleischmann
authors.forename: Scott N
authors.initials: SN
authors.lastname: Peterson
authors.forename: Saul
authors.initials: S
authors.lastname: Tzipori
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000032:analysis / Q000378:metabolism*; D019295:Computational Biology; D004405:Dysentery, Bacillary / Q000382:microbiology*; D015180:Electrophoresis, Gel, Two-Dimensional; D015964:Gene Expression Regulation, Bacterial; D007420:Intestine, Large / Q000382:microbiology; D013058:Mass Spectrometry; D020543:Proteome; D012762:Shigella dysenteriae / Q000378:metabolism* / Q000472:pathogenicity; D013552:Swine; D037521:Virulence Factors / Q000032:analysis* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D020543:Proteome; D037521:Virulence Factors