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Dynamics of Campylobacter jejuni and host responses in the porcine intestinal-loop infection model

Award Number: R21AI124144
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary Infection with Campylobacter jejuni is responsible for millions of cases of diarrhea per year and is a common precursor to Guillain-Barré syndrome, the leading cause of flaccid paralysis. Some individuals infected with C. jejuni experience watery diarrhea consisting of more than 10 stools per day whereas others suffer from inflammatory diarrhea with small-volume mucoid stool containing blood. It is currently uncertain whether the infectious C. jejuni strain, an individual's immune response, or both contribute to the variation in symptoms, severity, and duration of C. jejuni-mediated disease. Our central hypothesis is that the variation in clinical presentation associated with C. jejuni strains is, in part, due to differences in C. jejuni gene expression between strains. Invasive strains of C. jejuni cause bloody diarrhea whereas less-invasive strains cause diarrhea without blood (fewer of these bacteria invade and multiply in intestinal cells). We further hypothesize that infection with invasive strains of C. jejuni will result in greater host pro-inflammatory cytokines and Th17 cytokines (influence gut permeability) than infection with less-invasive strains. Finally, we hypothesize that C. jejuni infection (regardless of phenotypes) will result in a shift in the host-gut metabolism that, at least initially, favors its growth in the intestine. The novelty of this proposal is the use of the pig ligated-intestinal loop model to establish discrete replicative niches for four distinct (sequenced) C. jejuni strains in the intestinal lumen. Two of the C. jejuni strains to be tested in our model cause bloody diarrhea in pigs whereas two strains result in diarrhea without blood. Our preliminary studies have revealed that: 1) Significant genetic diversity exists amongst these four C. jejuni strains; and 2) C. jejuni synthesize a number of proteins either exclusively or preferentially when grown under host-like conditions (in the presence of epithelial cells or with a physiologically relevant concentration of the bile acid deoxycholate) as compared to nutrient broth, as judged by microarray (published) and RNA-Seq analysis (unpublished). In vivo studies are needed to determine the relationship between C. jejuni virulence gene expression and clinical disease presentation and to provide information regarding the complexity of the host response to different strains. The Specific Aims of this proposal are to: 1) Identify unique and/or differentially expressed genes using RNA extracted from C. jejuni cultured in the laboratory versus from C. jejuni collected from pig ligated-intestinal loops by transcriptomics. 2) Characterize the host response to infection with C. jejuni strains that cause bloody versus watery diarrhea. 3) Perform comparative metabolomics of luminal contents from uninfected and C. jejuni-infected loops.


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: 2020 ( Subtotal = -$127 )
2020	2018	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Allergy and Infectious Diseases Research	000	2	4/14/2020	NON-COMPETING CONTINUATION	-$127
														Subtotal = -$127

Issue Date FY: 2018 ( Subtotal = $185,324 )
2018	2018	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Allergy and Infectious Diseases Research	000	2	11/17/2017	NON-COMPETING CONTINUATION	$185,324
														Subtotal = $185,324

Issue Date FY: 2017 ( Subtotal = $234,227 )
2017	2017	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Allergy and Infectious Diseases Research	000	1	12/13/2016	NEW	$234,227
														Subtotal = $234,227

Grand Total All Awards = $419,424

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Dynamics of Campylobacter jejuni and host responses in the porcine intestinal-loop infection model

Award Number: R21AI124144

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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