Vibrio vulnificus is a natural inhabitant of coastal waters, including the US Gulf. The bacterium causes rapid septicemia after consumption of contaminated seafood (especially raw oysters), predominantly in persons with liver dysfunction. Among food-bourne pathogens, V. vulnificus is most notable for its high rates of hospitalization and death. Indeed, V. vulnificus accounts for 1% of deaths from food-bourne illness despite causing only 0.003% of illnesses. Although infections are rare, the number of serious infections has been increasing in recent years, possibly due to global warming that has caused a rise in the number of days amenable to growth of V. vulnificus in coastal waters. Attempts by the FDA to protect consumers by implementation of post-harvest processing mandates met with significant resistance from the shellfish harvesting industry forcing the FDA to review its policies. Thus, the study of V. vulnificus pathogenesis has become a food safety and public policy priority. Recent studies establish that cytotoxicity of V. vulnificus is predominantly associated with a large Multifunctional-Autoprocessing RTX toxin (MARTXVv). In this study, we demonstrate that this toxin is directly linked to pathogenesis by the intragastric route of infection, although its targets in vivo and molecular mechanism of action remain unknown. We propose to study the role of the MARTXVv toxin in pathogenesis using in vivo, cell culture, and biochemical systems. The focus of the proposal will be mechanisms directly impacting disease due to consumption of contaminated food and identification and characterization of specific regions of the toxin linked to cell lysis and increased virulence potential.

Public Health Relevance

Vibrio vulnificus is a bacterium that inhabits the US Gulf and causes sepsis and necrotizing fasciitis (flesh- eating bacteria). This study of V. vulnificus pathogenesis will specifically characterize a factor secreted by the bacterium that is linked to disease after consumption of contaminated food (especially oysters). When completed, this study will define how this factor contributes to food bourne infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI092825-05
Application #
8876353
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Hall, Robert H
Project Start
2011-07-01
Project End
2017-06-30
Budget Start
2015-07-01
Budget End
2017-06-30
Support Year
5
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
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Woida, Patrick J; Satchell, Karla J F (2018) Coordinated delivery and function of bacterial MARTX toxin effectors. Mol Microbiol 107:133-141
Gavin, Hannah E; Satchell, Karla J F (2018) RRSP and RID Effector Domains Dominate Virulence Impact of Vibrio vulnificus MARTX Toxin. J Infect Dis :
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Gavin, Hannah E; Beubier, Nike T; Satchell, Karla J F (2017) The Effector Domain Region of the Vibrio vulnificus MARTX Toxin Confers Biphasic Epithelial Barrier Disruption and Is Essential for Systemic Spread from the Intestine. PLoS Pathog 13:e1006119
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Biancucci, Marco; Rabideau, Amy E; Lu, Zeyu et al. (2017) Substrate Recognition of MARTX Ras/Rap1-Specific Endopeptidase. Biochemistry 56:2747-2757
Phillips, Kelsey E; Satchell, Karla J F (2017) Vibrio vulnificus: From Oyster Colonist to Human Pathogen. PLoS Pathog 13:e1006053

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