title: Genes contributing to Staphylococcus aureus fitness in abscess- and infection-related ecologies.
abstract: Staphylococcus aureus is a leading cause of both community- and hospital-acquired infections that are increasingly antibiotic resistant. The emergence of S. aureus resistance to even last-line antibiotics heightens the need for the development of new drugs with novel targets. We generated a highly saturated transposon insertion mutant library in the genome of S. aureus and used Tn-seq analysis to probe the entire genome, with unprecedented resolution and sensitivity, for genes of importance in infection. We further identified genes contributing to fitness in various infected compartments (blood and ocular fluids) and compared them to genes required for growth in rich medium. This resulted in the identification of 426 genes that were important for S. aureus fitness during growth in infection models, including 71 genes that could be considered essential for survival specifically during infection. These findings highlight novel as well as previously known genes encoding virulence traits and metabolic pathways important for S. aureus proliferation at sites of infection, which may represent new therapeutic targets.
  
  
  OBJECTIVE
  Staphylococcus aureus continues to be a leading cause of antibiotic-resistant community and nosocomial infection. With the bacterium's acquisition of resistance to methicillin and, more recently, vancomycin, the need for the development of new drugs with novel targets is urgent. Applying a highly saturated Tn-seq mutant library to analyze fitness and growth requirements in a murine abscess and in various infection-relevant fluids, we identified S. aureus traits that enable it to survive and proliferate during infection. This identifies potential new targeting opportunities for the development of novel therapeutics.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Valentino
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Lucy
authors.initials: L
authors.lastname: Foulston
authors.forename: Ama
authors.initials: A
authors.lastname: Sadaka
authors.forename: Veronica N
authors.initials: VN
authors.lastname: Kos
authors.affiliation: Division of Infectious Diseases and Medical Services, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Regis A
authors.initials: RA
authors.lastname: Villet
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: John
authors.initials: J
authors.lastname: Santa Maria
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Lazinski
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Camilli
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Walker
authors.affiliation: Division of Infectious Diseases and Medical Services, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Hooper
authors.affiliation: michael_gilmore@meei.harvard.edu.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Gilmore
mesh_terms: D000038:Abscess / Q000382:microbiology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D019295:Computational Biology; D004251:DNA Transposable Elements / Q000235:genetics; D024881:Drug Resistance, Bacterial; D015723:Gene Library; D016680:Genome, Bacterial; D008297:Male; D051379:Mice; D016372:RNA, Antisense / Q000235:genetics; D017422:Sequence Analysis, DNA; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000235:genetics*; D037521:Virulence Factors / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004251:DNA Transposable Elements; D016372:RNA, Antisense; D037521:Virulence Factors