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 #
1R01AI092825-01A1
Application #
8130113
Study Section
Special Emphasis Panel (ZRG1-IDM-T (02))
Program Officer
Hall, Robert H
Project Start
2011-07-01
Project End
2016-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
1
Fiscal Year
2011
Total Cost
$381,250
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
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
Biancucci, Marco; Dolores, Jazel S; Wong, Jennifer et al. (2017) New ligation independent cloning vectors for expression of recombinant proteins with a self-cleaving CPD/6xHis-tag. BMC Biotechnol 17:1
Gavin, Hannah E; Satchell, Karla J F (2017) Surface hypothermia predicts murine mortality in the intragastric Vibrio vulnificus infection model. BMC Microbiol 17:136
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
Kim, Byoung Sik; Gavin, Hannah E; Satchell, Karla J F (2017) Variable Virulence of Biotype 3 Vibrio vulnificus due to MARTX Toxin Effector Domain Composition. mSphere 2:
Song, Ha Yong; Biancucci, Marco; Kang, Hong-Jun et al. (2016) SIRT2 deletion enhances KRAS-induced tumorigenesis in vivo by regulating K147 acetylation status. Oncotarget 7:80336-80349
Kim, Byoung Sik; Satchell, Karla J F (2016) MARTX effector cross kingdom activation by Golgi-associated ADP-ribosylation factors. Cell Microbiol 18:1078-93
Satchell, Karla J F (2015) Multifunctional-autoprocessing repeats-in-toxin (MARTX) Toxins of Vibrios. Microbiol Spectr 3:
Antic, Irena; Biancucci, Marco; Zhu, Yueming et al. (2015) Site-specific processing of Ras and Rap1 Switch I by a MARTX toxin effector domain. Nat Commun 6:7396

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