Actinobacillus actinomycetemcomitans is a Gram-negative oral pathogen that is the etiologic agent of localized aggressive periodontitis. This bacterium can also cause several systemic diseases including infective endocarditis. As one of virulence factors, A. actinomycetemcomitans produces leukotoxin that kills human leukocytes and can also destroy erythrocytes. Our recent work strongly suggests that leukotoxin interacts with Cu, Zn superoxide dismutase (Cu, Zn SOD) from A. actinomycetemcomitans. Bacterial Cu, Zn SODs have a role in protecting pathogens from the oxidative damage caused by host inflamatory cells. Cu, Zn SOD has also been shown to bind heme and potentially play a role in iron and heme acquisition by bacteria. The proposed studies seek to understand the role of Cu, Zn SOD in A. actinomycetemcomitans. 1. I will study the interaction between Cu, Zn SOD and leukotoxin from A. actinomycetemcomitans. 2. I will characterize Cu, Zn SOD function in A. actinomycetemcomitans. This study will expand our knowledge of the physiology and pathogenesis of A. actinomycetemcomitans and may lead to a better understanding of the interplay between different putative virulence factors of an important oral pathogen.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DE017828-03
Application #
7413259
Study Section
NIDCR Special Grants Review Committee (DSR)
Program Officer
Frieden, Leslie A
Project Start
2006-05-01
Project End
2009-04-30
Budget Start
2008-05-01
Budget End
2009-04-30
Support Year
3
Fiscal Year
2008
Total Cost
$62,386
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Dentistry
Type
Schools of Dentistry
DUNS #
781265475
City
Newark
State
NJ
Country
United States
Zip Code
07101
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Balashova, Nataliya V; Shah, Chintan; Patel, Jigna K et al. (2009) Aggregatibacter actinomycetemcomitans LtxC is required for leukotoxin activity and initial interaction between toxin and host cells. Gene 443:42-7
Isaza, Maria P; Chau, Jennie T; Le, Amy et al. (2008) A bioluminescent HL-60 cell line to assay anti-leukaemia therapeutics under physiological conditions. Luminescence 23:17-21
Balashova, Nataliya V; Park, Diane H; Patel, Jigna K et al. (2007) Interaction between leukotoxin and Cu,Zn superoxide dismutase in Aggregatibacter actinomycetemcomitans. Infect Immun 75:4490-7
Balashova, Nataliya V; Diaz, Roger; Balashov, Sergey V et al. (2006) Regulation of Aggregatibacter (Actinobacillus) actinomycetemcomitans leukotoxin secretion by iron. J Bacteriol 188:8658-61