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.
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.
|Schwartz, Kelly; Ganesan, Mahesh; Payne, David E et al. (2016) Extracellular DNA facilitates the formation of functional amyloids in Staphylococcus aureus biofilms. Mol Microbiol 99:123-34|
|Syed, Adnan K; Reed, Tamra J; Clark, Kaitlyn L et al. (2015) Staphlyococcus aureus phenol-soluble modulins stimulate the release of proinflammatory cytokines from keratinocytes and are required for induction of skin inflammation. Infect Immun 83:3428-37|
|Abuaita, Basel H; Burkholder, Kristin M; Boles, Blaise R et al. (2015) The Endoplasmic Reticulum Stress Sensor Inositol-Requiring Enzyme 1Î± Augments Bacterial Killing through Sustained Oxidant Production. MBio 6:e00705|
|Stephenson, Rachel E; Gutierrez, Daniel; Peters, Cindy et al. (2014) Elucidation of bacteria found in car interiors and strategies to reduce the presence of potential pathogens. Biofouling 30:337-46|
|Staudinger, Benjamin J; Muller, Jocelyn Fraga; HalldÃ³rsson, SkarphÃ©Ã°inn et al. (2014) Conditions associated with the cystic fibrosis defect promote chronic Pseudomonas aeruginosa infection. Am J Respir Crit Care Med 189:812-24|
|Thoma, Laura M; Boles, Blaise R; Kuroda, Kenichi (2014) Cationic methacrylate polymers as topical antimicrobial agents against Staphylococcus aureus nasal colonization. Biomacromolecules 15:2933-43|
|DePas, William H; Syed, Adnan K; Sifuentes, Margarita et al. (2014) Biofilm formation protects Escherichia coli against killing by Caenorhabditis elegans and Myxococcus xanthus. Appl Environ Microbiol 80:7079-87|
|Schwartz, Kelly; Sekedat, Matthew D; Syed, Adnan K et al. (2014) The AgrD N-terminal leader peptide of Staphylococcus aureus has cytolytic and amyloidogenic properties. Infect Immun 82:3837-44|
|Syed, Adnan K; Boles, Blaise R (2014) Fold modulating function: bacterial toxins to functional amyloids. Front Microbiol 5:401|
|Syed, Adnan K; Ghosh, Sudeshna; Love, Nancy G et al. (2014) Triclosan promotes Staphylococcus aureus nasal colonization. MBio 5:e01015|
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