title: Proteomics uncovers extreme heterogeneity in the Staphylococcus aureus exoproteome due to genomic plasticity and variant gene regulation.
abstract: Sequencing of at least 13 Staphylococcus aureus isolates has shown that genomic plasticity impacts significantly on the repertoire of virulence factors. However, genome sequencing does not reveal which genes are expressed by individual isolates. Here, we have therefore performed a comprehensive survey of the composition and variability of the S. aureus exoproteome. This involved multilocus sequence typing, virulence gene, and prophage profiling by multiplex PCR, and proteomic analyses of secreted proteins using 2-DE. Dissection of the exoproteomes of 25 clinical isolates revealed that only seven out of 63 identified secreted proteins were produced by all isolates, indicating a remarkably high exoproteome heterogeneity within one bacterial species. Most interesting, the observed variations were caused not only by genome plasticity, but also by an unprecedented variation in secretory protein production due to differences in transcriptional and post-transcriptional regulation. Our data imply that genomic studies on virulence gene conservation patterns need to be complemented by analyses of the extracellular protein pattern to assess the full virulence potential of bacterial pathogens like S. aureus. Importantly, the extensive variability of secreted virulence factors in S. aureus also suggests that development of protective vaccines against this pathogen requires a carefully selected combination of invariably produced antigens.
authors.affiliation: Institute for Microbiology, University of Greifswald, Greifswald, Germany.
authors.forename: Anne-Kathrin
authors.initials: AK
authors.lastname: Ziebandt
authors.forename: Harald
authors.initials: H
authors.lastname: Kusch
authors.forename: Marco
authors.initials: M
authors.lastname: Degner
authors.forename: Sarah
authors.initials: S
authors.lastname: Jaglitz
authors.forename: Mark J J B
authors.initials: MJ
authors.lastname: Sibbald
authors.forename: Jan P
authors.initials: JP
authors.lastname: Arends
authors.forename: Monika A
authors.initials: MA
authors.lastname: Chlebowicz
authors.forename: Dirk
authors.initials: D
authors.lastname: Albrecht
authors.forename: Roman
authors.initials: R
authors.lastname: Pantucek
authors.forename: Jiri
authors.initials: J
authors.lastname: Doskar
authors.forename: Wilma
authors.initials: W
authors.lastname: Ziebuhr
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Bröker
authors.forename: Michael
authors.initials: M
authors.lastname: Hecker
authors.forename: Jan Maarten
authors.initials: JM
authors.lastname: van Dijl
authors.forename: Susanne
authors.initials: S
authors.lastname: Engelmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001426:Bacterial Proteins / Q000032:analysis* / Q000235:genetics; D002675:Child, Preschool; D015964:Gene Expression Regulation, Bacterial; D023281:Genomics; D006801:Humans; D007223:Infant; D008875:Middle Aged; D020543:Proteome / Q000032:analysis* / Q000235:genetics; D040901:Proteomics; D013211:Staphylococcus aureus / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D037521:Virulence Factors / Q000235:genetics; D055815:Young Adult
chemical_list: D001426:Bacterial Proteins; D020543:Proteome; D037521:Virulence Factors