Diarrheal diseases account for 650 million cases per year worldwide and 6 million children under 5 years old die each year due to acute gastrointestinal infection. Several pathotypes of diarrheagenic Escherichia coli [enteropathogenic (EPEC), enteroaggregative (EAEC), enterotoxigenic (ETEC)] play a major etiologic role in endemic areas. Enterohemorrhagic E. coli (EHEC) are associated with serious intestinal and kidney illness in developed countries due to consumption of tainted beef and agricultural products. The recent outbreaks caused in Northern Europe by a new EAEC O104:H4 producing the Shiga toxin highlight undoubtedly the significance of pathogenic E. coli and their ability to acquire virulence factors. The EAEC pathotype comprises a group of highly heterogenous E. coli strains, which share in common the ability to aggregate onto abiotic surfaces and epithelial cells forming a characteristic stacked-brick pattern. Their capacity to form dense biofilms may explain in part their ability to cause persistent diarrhea. Three aggregative adherence fimbriae (AAF/I-III) have been reported in EAEC but these are present in less than 15% of strains from different geographic regions. However, many other fimbrial operons exist that are shared with comnesal E. coli strains but little is known regarding their rol in adherence and biofilm formation. In this project we will provide insight into better understand the differential expression of these fimbrial operons and how they relate to adherence and biofilm formation. We expect to advance knowledge on the virulence mechanisms of pathogenic E. coli in general for the development of strategies towards prevention and treatment of diarrheal illnesses.

Public Health Relevance

Escherichia coli are food and water-borne bacteria responsible for high rates of diarrheal disease worldwide and a major cause of childhood mortality in developing countries. Enteroaggregative E. coli causes persistent mucoid diarrhea and the virulence factors are largely unknown. This proposal will study a new adherence factor of these bacteria aiming at identifying new targets for prevention of these infections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI111189-02
Application #
9070552
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Baqar, Shahida
Project Start
2015-05-20
Project End
2017-04-30
Budget Start
2016-05-01
Budget End
2017-04-30
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Virginia
Department
Pediatrics
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904