The principal investigator, (Dr. Boles), is currently a postdoctoral fellow at the University of Iowa. He has significant experience studying bacterial physiology and biofilm development in multiple pathogenic bacterial species. Within the next 12 months, he plans on obtaining a tenure track academic position at a major research institute with a future research focus on understanding S. aureus physiology and pathogenesis. The long-term objectives of his laboratory will be to understand the molecular mechanisms involved in S. aureus iron acquisition from mammalian host proteins and how these host proteins influence biofilm formation and dispersal. The proposed research will focus on elucidating how S. aureus obtains heme (and therefore iron) from hemoglobin and examining how hemoglobin influences S. aureus gene expression and biofilm development. Preliminary work has uncovered that S. aureus extracellular protease activity is necessary for iron acquisition from hemoglobin and hemoglobin can influence the production of S. aureus proteases.
The specific aims of this proposal are designed to 1) identify the specific S. aureus extracellular protease(s) necessary for heme acquisition from hemoglobin, 2) define the regulatory effects of hemoglobin on extracellular protease expression, and 3) examine the influence of hemoglobin on S. aureus biofilm formation. Dr. Boles'research plan has great relevance to public health as S. aureus is a major cause of infection and death in community and hospital associated infections. Findings from the proposed project will increase understanding of S. aureus pathogenic mechanisms and may lead to new therapeutic options for treating S. aureus infections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Career Transition Award (K22)
Project #
5K22AI081748-02
Application #
8019047
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Huntley, Clayton C
Project Start
2010-02-01
Project End
2012-05-31
Budget Start
2011-02-01
Budget End
2012-05-31
Support Year
2
Fiscal Year
2011
Total Cost
$108,000
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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
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
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
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
Payne, David E; Martin, Nicholas R; Parzych, Katherine R et al. (2013) Tannic acid inhibits Staphylococcus aureus surface colonization in an IsaA-dependent manner. Infect Immun 81:496-504
Schwartz, Kelly; Syed, Adnan K; Stephenson, Rachel E et al. (2012) Functional amyloids composed of phenol soluble modulins stabilize Staphylococcus aureus biofilms. PLoS Pathog 8:e1002744
Boles, Blaise R; Horswill, Alexander R (2011) Staphylococcal biofilm disassembly. Trends Microbiol 19:449-55
Pynnonen, Melissa; Stephenson, Rachel E; Schwartz, Kelly et al. (2011) Hemoglobin promotes Staphylococcus aureus nasal colonization. PLoS Pathog 7:e1002104
Boles, Blaise R; Thoendel, Matthew; Roth, Aleeza J et al. (2010) Identification of genes involved in polysaccharide-independent Staphylococcus aureus biofilm formation. PLoS One 5:e10146

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