Methicillin-resistant Staphylococcus aureus (MRSA) are a leading cause of infectious disease in the United States and elsewhere in the world;these bacteria have acquired resistance to all relevant classes of antibiotics and have become established in community and healthcare environments. Staphylococcus epidermidis and other coagulase-negative staphylococci, once exclusively considered to be commensal species, have emerged as a leading cause of infections associated with indwelling medical devices. Much of the human morbidity and mortality caused by staphylococci are due to a small number of successful, widespread clones. In the current proposal, we seek to exploit the power of rapid next-generation sequencing to obtain a more complete perspective of clone emergence and adaptation for several pathogenic staphylococci. Specifically, we will (1) elucidate fine-scale population structure and the origins, patterns of geographic spread, and evolution of clinically important traits of the USA300 MRSA clone, to characterize an ongoing epidemic, identify biomarkers of key variants, and provide baseline data for future epidemiological interventions;(2) validate coarse-scale population structure within pathogenic coagulase-negative species to identify novel biomarkers of pathogenic variants;(3) compare genome-wide targets of long-term positive selection in S. aureus and S. epidermidis and reveal the importance of balanced polymorphisms to specific antimicrobial resistances.

Public Health Relevance

Staphylococcus bacteria include established and emerging human pathogens. This proposal will analyze the DNA of some of the most pathogenic staphylococci, in order to reveal how strains emerge as pathogens and adapt to their human hosts. New molecular and analytical tools for identifying and tracking these strains will be generated, and new targets of potential diagnostic and therapeutic interest will be identified.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM080602-07A1
Application #
8503871
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Eckstrand, Irene A
Project Start
2007-03-01
Project End
2017-02-28
Budget Start
2013-04-15
Budget End
2014-02-28
Support Year
7
Fiscal Year
2013
Total Cost
$208,470
Indirect Cost
$69,025
Name
University of Mississippi Medical Center
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
928824473
City
Jackson
State
MS
Country
United States
Zip Code
39216
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