Group B streptococci continue to be a significant cause of morbidity and mortality in human neonates and other immunocompromised hosts. Although great strides have been made in understanding the mechanisms of host defense against these organisms, we still do not understand a great deal about the pathogenesis of this most fulminant of bacterial infections. We wish to concentrate on three aspects of the pathogenesis of, and immunity to group B streptococcal infection that we feel have exciting potential. First, we will seek to determine exactly what role fibronectin (FN) has in promoting epithelial cell adherence to group B streptococci. In addition, we will determine how FN enhances the opsonic activity of polyclonal and monoclonal antibody. Second, we will determine if the profound neutropenia and marrow granulocyte store depletion commonly observed in human and experimental animal group B disease is the result of decreased production of leukocyte mobilizing factors, such as C3e, derived from the complement system. Lastly, we will determine if group B streptococci or their soluble products affect vascular endothelial cell-neutrophil interactions and, thus, contribute to the pathogenesis of the lung damage in this serious and often overwhelming bacterial infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI013150-13
Application #
3125396
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1977-01-01
Project End
1991-03-31
Budget Start
1989-09-01
Budget End
1991-03-31
Support Year
13
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Utah
Department
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
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Joyner, J L; Augustine, N H; Taylor, K A et al. (2000) Effects of group B streptococci on cord and adult mononuclear cell interleukin-12 and interferon-gamma mRNA accumulation and protein secretion. J Infect Dis 182:974-7
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Jaskowski, T D; Martins, T B; Litwin, C M et al. (1999) Comparison of three different methods for measuring classical pathway complement activity. Clin Diagn Lab Immunol 6:137-9
Nester, T A; Wagnon, A H; Reilly, W F et al. (1998) Effects of allogeneic peripheral stem cell transplantation in a patient with job syndrome of hyperimmunoglobulinemia E and recurrent infections. Am J Med 105:162-4
Steele, P M; Augustine, N H; Hill, H R (1998) The effect of lactic acid on mononuclear cell secretion of proinflammatory cytokines in response to group B streptococci. J Infect Dis 177:1418-21
Takahashi, S; Adderson, E E; Nagano, Y et al. (1998) Identification of a highly encapsulated, genetically related group of invasive type III group B streptococci. J Infect Dis 177:1116-9
Bohnsack, J F; Widjaja, K; Ghazizadeh, S et al. (1997) A role for C5 and C5a-ase in the acute neutrophil response to group B streptococcal infections. J Infect Dis 175:847-55

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