title: Mapping the protein interaction network in methicillin-resistant Staphylococcus aureus.
abstract: Mortality attributable to infection with methicillin-resistant Staphylococcus aureus (MRSA) has now overtaken the death rate for AIDS in the United States, and advances in research are urgently needed to address this challenge. We report the results of the systematic identification of protein-protein interactions for the hospital-acquired strain MRSA-252. Using a high-throughput pull-down strategy combined with quantitative proteomics to distinguish specific from nonspecific interactors, we identified 13,219 interactions involving 608 MRSA proteins. Consecutive analyses revealed that this protein interaction network (PIN) exhibits scale-free organization with the characteristic presence of highly connected hub proteins. When clinical and experimental antimicrobial targets were queried in the network, they were generally found to occupy peripheral positions in the PIN with relatively few interacting partners. In contrast, the hub proteins identified in this MRSA PIN that are essential for network integrity and stability have largely been overlooked as drug targets. Thus, this empirical MRSA-252 PIN provides a rich source for identifying critical proteins essential for network stability, many of which can be considered as prospective antimicrobial drug targets.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. artc@interchange.ubc.ca
authors.forename: Artem
authors.initials: A
authors.lastname: Cherkasov
authors.forename: Michael
authors.initials: M
authors.lastname: Hsing
authors.forename: Roya
authors.initials: R
authors.lastname: Zoraghi
authors.forename: Leonard J
authors.initials: LJ
authors.lastname: Foster
authors.forename: Raymond H
authors.initials: RH
authors.lastname: See
authors.forename: Nikolay
authors.initials: N
authors.lastname: Stoynov
authors.forename: Jihong
authors.initials: J
authors.lastname: Jiang
authors.forename: Sukhbir
authors.initials: S
authors.lastname: Kaur
authors.forename: Tian
authors.initials: T
authors.lastname: Lian
authors.forename: Linda
authors.initials: L
authors.lastname: Jackson
authors.forename: Huansheng
authors.initials: H
authors.lastname: Gong
authors.forename: Rick
authors.initials: R
authors.lastname: Swayze
authors.forename: Emily
authors.initials: E
authors.lastname: Amandoron
authors.forename: Farhad
authors.initials: F
authors.lastname: Hormozdiari
authors.forename: Phuong
authors.initials: P
authors.lastname: Dao
authors.forename: Cenk
authors.initials: C
authors.lastname: Sahinalp
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Santos-Filho
authors.forename: Peter
authors.initials: P
authors.lastname: Axerio-Cilies
authors.forename: Kendall
authors.initials: K
authors.lastname: Byler
authors.forename: William R
authors.initials: WR
authors.lastname: McMaster
authors.forename: Robert C
authors.initials: RC
authors.lastname: Brunham
authors.forename: B Brett
authors.initials: BB
authors.lastname: Finlay
authors.forename: Neil E
authors.initials: NE
authors.lastname: Reiner
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry; D055624:Methicillin-Resistant Staphylococcus aureus / Q000737:chemistry* / Q000378:metabolism*; D025941:Protein Interaction Mapping / Q000379:methods*; D040901:Proteomics / Q000379:methods; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013203:Staphylococcal Infections / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D011993:Recombinant Fusion Proteins