title: Staphylococcus aureus genetic loci impacting growth and survival in multiple infection environments.
abstract: The Gram-positive bacterium Staphylococcus aureus infects diverse tissues and causes a wide spectrum of diseases, suggesting that it possesses a repertoire of distinct molecular mechanisms promoting bacterial survival in disparate in vivo environments. Signature-tag transposon mutagenesis screening of a 1520-member library identified numerous S. aureus genetic loci affecting growth and survival in four complementary animal infection models including mouse abscess, bacteraemia and wound and rabbit endocarditis. Of a total of 237 in vivo attenuated mutants identified by the murine models, less than 10% showed attenuation in all three models, emphasizing the advantage of screening in diverse disease environments. The largest gene class identified by these analyses encoded peptide and amino acid transporters, some of which were important for S. aureus survival in all animal infection models tested. The identification of staphylococcal loci affecting growth, persistence and virulence in multiple tissue environments provides insight into the complexities of human infection and on the molecular mechanisms that could be targeted by new antibacterial therapies.
authors.affiliation: PathoGenesis Corporation, 201 Elliott Avenue West, Seattle, WA 98119, USA.
authors.forename: S N
authors.initials: SN
authors.lastname: Coulter
authors.forename: W R
authors.initials: WR
authors.lastname: Schwan
authors.forename: E Y
authors.initials: EY
authors.lastname: Ng
authors.forename: M H
authors.initials: MH
authors.lastname: Langhorne
authors.forename: H D
authors.initials: HD
authors.lastname: Ritchie
authors.forename: S
authors.initials: S
authors.lastname: Westbrock-Wadman
authors.forename: W O
authors.initials: WO
authors.lastname: Hufnagle
authors.forename: K R
authors.initials: KR
authors.lastname: Folger
authors.forename: A S
authors.initials: AS
authors.lastname: Bayer
authors.forename: C K
authors.initials: CK
authors.lastname: Stover
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D016470:Bacteremia / Q000382:microbiology; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000235:genetics; D004195:Disease Models, Animal; D004696:Endocarditis / Q000382:microbiology; D015723:Gene Library; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D011817:Rabbits; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity*; D014774:Virulence; D014947:Wounds and Injuries / Q000382:microbiology
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D002352:Carrier Proteins; C115788:Opp-1 protein, Staphylococcus aureus; C115789:Opp-2 protein, Staphylococcus aureus