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Research Article

Genes Contributing to Staphylococcus aureus Fitness in Abscess- and Infection-Related Ecologies

Michael D. Valentino, Lucy Foulston, Ama Sadaka, Veronica N. Kos, Regis A. Villet, John Santa Maria Jr., David W. Lazinski, Andrew Camilli, Suzanne Walker, David C. Hooper, Michael S. Gilmore
Larry S. McDaniel, Editor
Michael D. Valentino
aDepartment of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA
bDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA
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Lucy Foulston
cDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA
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Ama Sadaka
aDepartment of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA
bDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA
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Veronica N. Kos
aDepartment of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA
bDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA
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Regis A. Villet
dDivision of Infectious Diseases and Medical Services, Massachusetts General Hospital, Boston, Massachusetts, USA
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John Santa Maria Jr.
bDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA
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David W. Lazinski
eDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA
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Andrew Camilli
eDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA
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Suzanne Walker
bDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA
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David C. Hooper
dDivision of Infectious Diseases and Medical Services, Massachusetts General Hospital, Boston, Massachusetts, USA
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Michael S. Gilmore
aDepartment of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA
bDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA
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Larry S. McDaniel
University of Mississippi
Roles: Editor
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DOI: 10.1128/mBio.01729-14
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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.

IMPORTANCE 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.

FOOTNOTES

    • Received 30 July 2014
    • Accepted 6 August 2014
    • Published 2 September 2014
  • Copyright © 2014 Valentino et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Genes Contributing to Staphylococcus aureus Fitness in Abscess- and Infection-Related Ecologies
Michael D. Valentino, Lucy Foulston, Ama Sadaka, Veronica N. Kos, Regis A. Villet, John Santa Maria Jr., David W. Lazinski, Andrew Camilli, Suzanne Walker, David C. Hooper, Michael S. Gilmore
mBio Sep 2014, 5 (5) e01729-14; DOI: 10.1128/mBio.01729-14

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Genes Contributing to Staphylococcus aureus Fitness in Abscess- and Infection-Related Ecologies
Michael D. Valentino, Lucy Foulston, Ama Sadaka, Veronica N. Kos, Regis A. Villet, John Santa Maria Jr., David W. Lazinski, Andrew Camilli, Suzanne Walker, David C. Hooper, Michael S. Gilmore
mBio Sep 2014, 5 (5) e01729-14; DOI: 10.1128/mBio.01729-14
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