title: A proteomic view of an important human pathogen--towards the quantification of the entire Staphylococcus aureus proteome.
abstract: The genome sequence is the "blue-print of life," but proteomics provides the link to the actual physiology of living cells. Because of their low complexity bacteria are excellent model systems to identify the entire protein assembly of a living organism. Here we show that the majority of proteins expressed in growing and non-growing cells of the human pathogen Staphylococcus aureus can be identified and even quantified by a metabolic labeling proteomic approach. S. aureus has been selected as model for this proteomic study, because it poses a major risk to our health care system by combining high pathogenicity with an increasing frequency of multiple antibiotic resistance, thus requiring the development of new anti-staphylococcal therapy strategies. Since such strategies will likely have to target extracellular and surface-exposed virulence factors as well as staphylococcal survival and adaptation capabilities, we decided to combine four subproteomic fractions: cytosolic proteins, membrane-bound proteins, cell surface-associated and extracellular proteins, to comprehensively cover the entire proteome of S. aureus. This quantitative proteomics approach integrating data ranging from gene expression to subcellular localization in growing and non-growing cells is a proof of principle for whole-cell physiological proteomics that can now be extended to address physiological questions in infection-relevant settings. Importantly, with more than 1700 identified proteins (and 1450 quantified proteins) corresponding to a coverage of about three-quarters of the expressed proteins, our model study represents the most comprehensive quantification of a bacterial proteome reported to date. It thus paves the way towards a new level in understanding of cell physiology and pathophysiology of S. aureus and related pathogenic bacteria, opening new avenues for infection-related research on this crucial pathogen.
authors.affiliation: Institute for Microbiology, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.
authors.forename: Dörte
authors.initials: D
authors.lastname: Becher
authors.forename: Kristina
authors.initials: K
authors.lastname: Hempel
authors.forename: Susanne
authors.initials: S
authors.lastname: Sievers
authors.forename: Daniela
authors.initials: D
authors.lastname: Zühlke
authors.forename: Jan
authors.initials: J
authors.lastname: Pané-Farré
authors.forename: Andreas
authors.initials: A
authors.lastname: Otto
authors.forename: Stephan
authors.initials: S
authors.lastname: Fuchs
authors.forename: Dirk
authors.initials: D
authors.lastname: Albrecht
authors.forename: Jörg
authors.initials: J
authors.lastname: Bernhardt
authors.forename: Susanne
authors.initials: S
authors.lastname: Engelmann
authors.forename: Uwe
authors.initials: U
authors.lastname: Völker
authors.forename: Jan Maarten
authors.initials: JM
authors.lastname: van Dijl
authors.forename: Michael
authors.initials: M
authors.lastname: Hecker
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D020543:Proteome / Q000032:analysis* / Q000235:genetics; D040901:Proteomics / Q000379:methods*; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; D020543:Proteome