Staphylococcus aureus is a medically important human pathogen that is found in the nasal passages of approximately 1/3 of the human population. The nose serves as a reservoir for spread of this pathogen and predisposes the host to potential infection. Despite the importance of S. aureus to human health, molecular mechanisms and host factors influencing nasal colonization are not well understood. We have recently discovered an extracellular amyloid fiber produced by S. aureus during nasal colonization. This finding is extremely novel and exciting as S. aureus has never been shown to produce extracellular structures. We hypothesize that this extracellular fiber is important for S. aureus nasal colonization and persistence within the nose. Our preliminary results suggest that the fibers contribute to biofilm development and consist of multiple toxins, which are folding into beta sheet rich confirmations to self-assemble into amyloid fibers.
The aims of this proposal will determine the composition, formation, degradation and role of S. aureus fibers during nasal colonization and biofilm development. At the conclusion of these studies, we will have expanded our knowledge of S. aureus nasal colonization and characterized a novel extracellular structure produced by this important commensal and pathogen.

Public Health Relevance

Staphylococcus aureus nasal colonization is a very common and a risk factor for developing severe infections. Molecular mechanisms utilized by S. aureus to colonize the nose and host factors influencing colonization are only beginning to be elucidated. This project investigates the role of a newly described extracellular amyloid fiber made by S. aureus during nasal colonization. The proposal specifically focuses on defining the composition, formation, degradation and role of S. aureus fibers during nasal colonization and biofilm development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI099065-04
Application #
8758820
Study Section
Bacterial Pathogenesis Study Section (BACP)
Program Officer
Huntley, Clayton C
Project Start
2012-12-01
Project End
2017-11-30
Budget Start
2014-12-01
Budget End
2015-11-30
Support Year
4
Fiscal Year
2015
Total Cost
$377,500
Indirect Cost
$127,500
Name
University of Iowa
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
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