This is an application by Victor Nizet, M.D. for a KO8 award for mentored studies under the direction of Craig Rubens, M.D., in the Department of Pediatrics, Washington University and the Children's Hospital and Medical Center, Seattle, WA. Dr. Nizet is an acting instructor in the Department of Pediatrics, Children s Hospital, Seattle, Washington. Dr. Nizet obtained his M.D. in 1989 from Stanford University. Dr. Craig Rubens will act as mentor. Dr. Rubens is Associate Professor of Pediatrics. He obtained a Ph.D. in microbiology from the Medical University of South Carolina in 1978 and M.D. from the University of Washington in 1982. Dr. Nizet will examine the role of beta hemolysin in group B streptococcal infections and its ability to cause cellular damage in the lung. His studies will focus on the identification of the genes involved in the regulation and structure of this lysin, and in vitro and in vivo pathogenesis studies using group B streptococci with knock-outs in these genes. The proposed studies are based on successful preliminary studies in which Dr. Nizet has made TN916, TN917, and chemical mutagenesis mutants that resulted in elevated and diminished levels of hemolysin. He has also prepared site directed mutants in group B streptococci to test the possibility that a known group B hemolysin might be the major group B hemolysin. He found that it was not. His """"""""training plan"""""""" appears to primarily constitute protection of 85% of this time for research training. He proposes to develop molecular, genetic, and pathogenesis skills required for his studies. In particular he will learn techniques involved in cloning and sequencing DNA, preparing knock out mutants, conducting rigorous evaluation of the validity of molecular and genetic techniques, and applying them to in vitro and in vivo models of infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AI001451-03
Application #
2671449
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Project Start
1997-04-01
Project End
2001-03-31
Budget Start
1998-04-01
Budget End
1999-03-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Pediatrics
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Hensler, Mary E; Quach, Darin; Hsieh, Chia-Jun et al. (2008) CAMP factor is not essential for systemic virulence of Group B Streptococcus. Microb Pathog 44:84-8
Humar, Deepali; Datta, Vivekananda; Bast, Darrin J et al. (2002) Streptolysin S and necrotising infections produced by group G streptococcus. Lancet 359:124-9
Ring, Axel; Braun, Johann S; Pohl, Jurgen et al. (2002) Group B streptococcal beta-hemolysin induces mortality and liver injury in experimental sepsis. J Infect Dis 185:1745-53
Nizet, Victor (2002) Streptococcal beta-hemolysins: genetics and role in disease pathogenesis. Trends Microbiol 10:575-80
Doran, Kelly S; Chang, Jennifer C W; Benoit, Vivian M et al. (2002) Group B streptococcal beta-hemolysin/cytolysin promotes invasion of human lung epithelial cells and the release of interleukin-8. J Infect Dis 185:196-203
Pritzlaff, C A; Chang, J C; Kuo, S P et al. (2001) Genetic basis for the beta-haemolytic/cytolytic activity of group B Streptococcus. Mol Microbiol 39:236-47
Nizet, V; Beall, B; Bast, D J et al. (2000) Genetic locus for streptolysin S production by group A streptococcus. Infect Immun 68:4245-54
Ring, A; Braun, J S; Nizet, V et al. (2000) Group B streptococcal beta-hemolysin induces nitric oxide production in murine macrophages. J Infect Dis 182:150-7
Puliti, M; Nizet, V; von Hunolstein, C et al. (2000) Severity of group B streptococcal arthritis is correlated with beta-hemolysin expression. J Infect Dis 182:824-32
Gibson, R L; Nizet, V; Rubens, C E (1999) Group B streptococcal beta-hemolysin promotes injury of lung microvascular endothelial cells. Pediatr Res 45:626-34

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