Infections caused by Staphylococcus aureus span a wide clinical spectrum, ranging from asymptomatic nasal carriage to endocarditis, bone and joint infections and lethal shock. Increasing rates of S. aureus infection and the emergence of community-acquired strains drive the need for an increased understanding of the virulence determinants of this emerging pathogen and evaluating the role they play in outcome of patients with S. aureus bacteremia. Evaluating the role of these virulence determinants in humans was limited by the absence of a large, well-characterized collection of bloodstream S. aureus isolates. Such a clinical resource was developed by Vance Fowler (Co-Investigator), when he created one of the world

Public Health Relevance

Genetic factors in Staphylococcus aureus play a critical role in causing and determining the severity of infection and disease. This study proposes to identify these variations in a large collection of clinically isolated, disease-causing Staphylococci by examining genes known to be involved and identifying new genes that may be involved in infection. Knowledge acquired from this study could potentially be used to develop novel and possibly preventive therapies to eradicate complicated staphylococcal infections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI059111-07
Application #
8324498
Study Section
Bacterial Pathogenesis Study Section (BACP)
Program Officer
Huntley, Clayton C
Project Start
2011-09-01
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2014-08-31
Support Year
7
Fiscal Year
2012
Total Cost
$633,847
Indirect Cost
$185,334
Name
University of Rochester
Department
Internal Medicine/Medicine
Type
Schools of Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627
Canfield, Gregory S; Schwingel, Johanna M; Foley, Matthew H et al. (2013) Evolution in fast forward: a potential role for mutators in accelerating Staphylococcus aureus pathoadaptation. J Bacteriol 195:615-28
Gill, Steven R; McIntyre, Lauren M; Nelson, Charlotte L et al. (2011) Potential associations between severity of infection and the presence of virulence-associated genes in clinical strains of Staphylococcus aureus. PLoS One 6:e18673
Gerrish, Robert S; Gill, Ann L; Fowler, Vance G et al. (2010) Development of pooled suppression subtractive hybridization to analyze the pangenome of Staphylococcus aureus. J Microbiol Methods 81:56-60
Gerrish, Robert S; Gill, Steven R (2010) Tailed pooled suppression subtractive hybridization (PSSH) adaptors do not alter efficiency. Antonie Van Leeuwenhoek 98:573-9
Xiong, Yan Q; Fowler, Vance G; Yeaman, Michael R et al. (2009) Phenotypic and genotypic characteristics of persistent methicillin-resistant Staphylococcus aureus bacteremia in vitro and in an experimental endocarditis model. J Infect Dis 199:201-8
Bae, In-Gyu; Federspiel, Jerome J; Miro, Jose M et al. (2009) Heterogeneous vancomycin-intermediate susceptibility phenotype in bloodstream methicillin-resistant Staphylococcus aureus isolates from an international cohort of patients with infective endocarditis: prevalence, genotype, and clinical significance. J Infect Dis 200:1355-66
Stryjewski, Martin E; Szczech, Lynda A; Benjamin Jr, Daniel K et al. (2007) Use of vancomycin or first-generation cephalosporins for the treatment of hemodialysis-dependent patients with methicillin-susceptible Staphylococcus aureus bacteremia. Clin Infect Dis 44:190-6
Aksoy, Olcay; Sexton, Daniel J; Wang, Andrew et al. (2007) Early surgery in patients with infective endocarditis: a propensity score analysis. Clin Infect Dis 44:364-72
Fowler Jr, Vance G; Nelson, Charlotte L; McIntyre, Lauren M et al. (2007) Potential associations between hematogenous complications and bacterial genotype in Staphylococcus aureus infection. J Infect Dis 196:738-47
Inrig, Jula K; Reed, Shelby D; Szczech, Lynda A et al. (2006) Relationship between clinical outcomes and vascular access type among hemodialysis patients with Staphylococcus aureus bacteremia. Clin J Am Soc Nephrol 1:518-24

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