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Regulation of the Poly Sialic Virulence Factor

Award Number: R01AI042015
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/1998
PERIOD OF PERFORMANCE END DATE: 04/30/2015

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Regulation of the Poly Sialic Virulence Factor - DESCRIPTION (provided by applicant): Extraintestinal pathogenic Escherichia coli (ExPEC) are major pathogens in mostly the very young, aged or immunocompromised human population resulting in tens of thousands of deaths each year and billions of dollars in healthcare costs. For example, the predominant ExPEC subtype, E. coli O18:K1, expresses O18 somatic and K1 polysialic acid capsule antigens as two major virulence factors responsible for making these strains the leading causes of neonatal bacterial meningitis. Using microbial genetics and innovative methods of carbohydrate analysis, we defined the complete pathways for sialic acid transport, synthesis, polymerization, catabolism and modification of both monomeric and polysialic acids. The modification mechanism was linked to a novel bacterial virus (CUS-3) carrying the phase-variable acetylase gene catalyzing stochastic O-acetylation of the sialic acid exocyclic chain. We hypothesize that understanding the in vivo functions of these bacterial antigens will facilitate approaches targeting them for new therapeutic development. We have designed three specific aims to test this hypothesis: 1) Determine the contribution of monomeric sialic acid O- acetylation to overall polysialic acid modification by genetically altering the acetyltransferase, NeuD, and acetylesterase, NeuA* (NeuA-star). This aim focuses on the enzymes involved in the reciprocal addition (NeuD) or subtraction (NeuA*) of O- acetyl esters to or from monomeric sialic acids prior to their incorporation into polysialic acid. 2) Determine the dynamics of capsular polysialic acid modification in vivo using an innovative flow cytometric technique and microscopic methods to distinguish between acetylated and unacetylated phases in different host compartments. 3) Determine the molecular basis for coupling polysaccharide synthesis to export by (i) constructing in frame deletions of all region 1 export genes, (ii) determining whether 3-deoxy-D-manno- octulosonate is required for biosynthesis, (iii) identifying the polymerase domain(s) interacting with the accessory protein, KpsC, (iv) using Quantum-dot technology and K1- specific phage to determine the site of capsule export, and (v) determining the chemical structure of the initiation complex.


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: 2014 ( Subtotal = $235,373 )
2014	2014	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Allergy and Infectious Diseases Research	000	15	7/9/2014	NON-COMPETING CONTINUATION	$235,373
														Subtotal = $235,373

Issue Date FY: 2013 ( Subtotal = $221,250 )
2013	2013	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Allergy and Infectious Diseases Research	001	14	6/4/2013	NON-COMPETING CONTINUATION	$9,415
2013	2013	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Allergy and Infectious Diseases Research	000	14	4/4/2013	NON-COMPETING CONTINUATION	$211,835
														Subtotal = $221,250

Issue Date FY: 2012 ( Subtotal = $235,373 )
2012	2012	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Allergy and Infectious Diseases Research	000	13	4/9/2012	NON-COMPETING CONTINUATION	$235,373
														Subtotal = $235,373

Issue Date FY: 2011 ( Subtotal = $235,373 )
2011	2011	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Allergy and Infectious Diseases Research	001	12	6/10/2011	NON-COMPETING CONTINUATION	$21,398
2011	2011	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Allergy and Infectious Diseases Research	000	12	4/27/2011	NON-COMPETING CONTINUATION	$213,975
														Subtotal = $235,373

Issue Date FY: 2010 ( Subtotal = $217,938 )
2010	2010	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Allergy and Infectious Diseases Research	000	11	4/21/2010	COMPETING CONTINUATION	$217,938
														Subtotal = $217,938

Issue Date FY: 2009 ( Subtotal = $0 )
2009	2008	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Allergy and Infectious Diseases Research	000	10	5/26/2009	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2008 ( Subtotal = $177,895 )
2008	2008	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Allergy and Infectious Diseases Research	000	10	11/21/2007	NON-COMPETING CONTINUATION	$177,895
														Subtotal = $177,895

Issue Date FY: 2007 ( Subtotal = $181,340 )
2007	2007	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Allergy and Infectious Diseases Research	000	9	12/11/2006	NON-COMPETING CONTINUATION	$181,340
														Subtotal = $181,340

Issue Date FY: 2006 ( Subtotal = $186,756 )
2006	2006	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Allergy and Infectious Diseases Research	000	8	12/15/2005	NON-COMPETING CONTINUATION	$186,756
														Subtotal = $186,756

Issue Date FY: 2005 ( Subtotal = $191,250 )
2005	2005	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Microbiology and Infectious Diseases Research	000	7	12/22/2004	NON-COMPETING CONTINUATION	$191,250
														Subtotal = $191,250

Issue Date FY: 2004 ( Subtotal = $191,250 )
2004	2004	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Microbiology and Infectious Diseases Research	000	6	12/22/2003	COMPETING CONTINUATION	$191,250
														Subtotal = $191,250

Issue Date FY: 2002 ( Subtotal = $173,947 )
2002	2002	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Microbiology and Infectious Diseases Research	000	5	5/14/2002	NON-COMPETING CONTINUATION	$173,947
														Subtotal = $173,947

Issue Date FY: 2001 ( Subtotal = $168,877 )
2001	2001	UNIVERSITY OF ILLINOIS URBANA CAMPUS	809 SOUTH WRIGHT STREET	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Microbiology and Infectious Diseases Research	000	4	4/16/2001	NON-COMPETING CONTINUATION	$168,877
														Subtotal = $168,877

Issue Date FY: 2000 ( Subtotal = $163,962 )
2000	2000	UNIVERSITY OF ILLINOIS URBANA CAMPUS	809 SOUTH WRIGHT STREET	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Microbiology and Infectious Diseases Research	000	3	5/8/2000	NON-COMPETING CONTINUATION	$163,962
														Subtotal = $163,962

Issue Date FY: 1999 ( Subtotal = $159,186 )
1999	1999	UNIVERSITY OF ILLINOIS URBANA CAMPUS	809 SOUTH WRIGHT STREET	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Microbiology and Infectious Diseases Research	000	2	5/5/1999	NON-COMPETING CONTINUATION	$159,186
														Subtotal = $159,186

Issue Date FY: 1998 ( Subtotal = $174,567 )
1998	1998	UNIVERSITY OF ILLINOIS URBANA CAMPUS	809 SOUTH WRIGHT STREET	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Microbiology and Infectious Diseases Research	000	1	6/15/1998	NEW	$174,567
														Subtotal = $174,567

Grand Total All Awards = $2,914,337

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Regulation of the Poly Sialic Virulence Factor

Award Number: R01AI042015

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/1998

PERIOD OF PERFORMANCE END DATE: 04/30/2015

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