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CHARACTERIZATION OF A. ACTINOMYCETEMCOMITANS LEUKOTOXIN MUTANTS

Award Number: F31DE018099
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 03/01/2007
PERIOD OF PERFORMANCE END DATE: 02/28/2009

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CHARACTERIZATION OF A. ACTINOMYCETEMCOMITANS LEUKOTOXIN MUTANTS - DESCRIPTION (provided by applicant): A. actinomycetemcomitans, a gram-negative bacterium, is the causative agent of localized aggressive periodontitis (LAP). A. actinomycetemcomitans is also a member of the important HACECK group of bacteria implicated in enfective endocarditis. One of its virulence factors, a potent leukotoxin, kills specifically white blood cells and can also destroy erythrocytes. Leukotoxin is a member of the RTX toxins. Much of the present knowledge in the biosynthesis of leukotoxin in A. actinomycetemcomitans is based on similarity with other bacterial systems, such as E. coli, but some differences exist between those systems and A. actinomycetemcomitans. We propose to study the biosynthesis of leukotoxin in A. actinomycetemcomitans to expand our knowledge of the physiology and pathogenesis of this organism which can lead to a better understanding of the role played by leukotoxin as virulence factor. More specifically, we propose studies that aim to: 1. Characterize of novel genes involved in leukotoxin biosynthersis. We have isolated leukotoxin mutants, and several mutations map somewhere outside of the leukotoxin operon. We propose experiments that will identify and characterize the nature of the mutations. 2. Determine the function of ItxC in the modification and activiy of leukotoxin. We propose experiments that will allow us to study modification of leukotoxin in ItxC mutants and to determine the role of ItxC on the activity of leukotoxin. This study will expand our knowledge of the genetics of leukotoxin production in A. actinomycetemcomitans. A. actinomycetemcomitans, an oral pathogen, causes periodontal and heart disease. We are studying the genetics involved in the synthesis of a toxin produced by this bacterium. It is our goal to understand the role played by this toxin in the disease with the hopes of enhancing our ability to prevent or treat diseases caused by A. actinomycetemcomitans.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2008 ( Subtotal = $33,572 )
2008	2008	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	65 BERGEN STREET	NEWARK	NJ	07101	ESSEX	USA	Oral Diseases and Disorders Research	000	2	1/17/2008	NON-COMPETING CONTINUATION	$33,572
														Subtotal = $33,572

Issue Date FY: 2007 ( Subtotal = $33,572 )
2007	2007	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	65 BERGEN STREET	NEWARK	NJ	07101	ESSEX	USA	Oral Diseases and Disorders Research	000	1	3/1/2007	NEW	$33,572
														Subtotal = $33,572

Grand Total All Awards = $67,144

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CHARACTERIZATION OF A. ACTINOMYCETEMCOMITANS LEUKOTOXIN MUTANTS

Award Number: F31DE018099

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 03/01/2007

PERIOD OF PERFORMANCE END DATE: 02/28/2009

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