Streptococcal pathogens continue to evade concerted efforts to decipher clear-cut virulence mechanisms, although numerous genes have been implicated in pathogenesis. A single species can infect a diversity of tissues, suggesting the expression of specific virulence factors based on the local tissue environment or stage of infection. Our long-range goal is to identify the interactions that occur between the host and pathogen that lead to activation of virulence mechanisms and contribute to specific streptococcal disease states. The objective of this application is to characterize specific virulence mechanisms utilized within various tissues in vivo by employing a unique animal model, the zebrafish (Danio rerio). We will accomplish this by studying infection by two streptococcal species that represent two forms of streptococcal disease: a natural pathogen of both fish and humans, Streptococcus iniae, and a human-specific pathogen, Streptococcus pyogenes. While S. iniae primarily causes systemic disease in the zebrafish following intra-muscular injection, S. pyogenes causes a locally spreading necrotic disease confined to the muscle. By studying pathogens that are virulent for both fish and humans and that mediate disease states in the zebrafish that are identical to those found in human streptococcal infections, we will be able to identify common virulence strategies shared by a number of Gram positive pathogens. The central hypothesis is that streptococcal pathogens respond to their host by initiating specific virulence mechanisms based on the local tissue environment or host-specific factors expressed within that tissue. We propose to: (1) identify and characterize bacterial proteins that interact with the host in vivo to cause specific disease states and (2) characterize the role in pathogenesis of proteins previously implicated in virulence. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
3R01AI052141-04S1
Application #
7234651
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Rubin, Fran A
Project Start
2003-02-15
Project End
2008-01-31
Budget Start
2006-06-01
Budget End
2008-01-31
Support Year
4
Fiscal Year
2006
Total Cost
$38,602
Indirect Cost
Name
Wayne State University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
001962224
City
Detroit
State
MI
Country
United States
Zip Code
48202
Rowe, Hannah M; Withey, Jeffrey H; Neely, Melody N (2014) Zebrafish as a model for zoonotic aquatic pathogens. Dev Comp Immunol 46:96-107
Hanson, Brett R; Neely, Melody N (2012) Coordinate regulation of Gram-positive cell surface components. Curr Opin Microbiol 15:204-10
Allen, Jonathan P; Neely, Melody N (2010) Trolling for the ideal model host: zebrafish take the bait. Future Microbiol 5:563-9
Kizy, Anne E; Neely, Melody N (2009) First Streptococcus pyogenes signature-tagged mutagenesis screen identifies novel virulence determinants. Infect Immun 77:1854-65
Phelps, Hilary A; Runft, Donna L; Neely, Melody N (2009) Adult zebrafish model of streptococcal infection. Curr Protoc Microbiol Chapter 9:Unit 9D.1