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. 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. 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 early infection after consumption of contaminated food and identification and characterization of specific regions of the toxin linked to tissue damage and immune system evasion.

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 virulence 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 #
5R01AI098369-03
Application #
8586298
Study Section
Special Emphasis Panel (ZRG1-IDM-R (02))
Program Officer
Hall, Robert H
Project Start
2011-12-01
Project End
2016-11-30
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
3
Fiscal Year
2014
Total Cost
$227,994
Indirect Cost
$76,024
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
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 :
Biancucci, Marco; Minasov, George; Banerjee, Avik et al. (2018) The bacterial Ras/Rap1 site-specific endopeptidase RRSP cleaves Ras through an atypical mechanism to disrupt Ras-ERK signaling. Sci Signal 11:
Trinh, Sonya A; Leyn, Semen A; Rodionov, Ivan D et al. (2018) Draft Genome Sequences of Two Vibrio parahaemolyticus Strains Associated with Gastroenteritis after Raw Seafood Ingestion in Colorado. Genome Announc 6:
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
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; 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
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
Trinh, Sonya A; Gavin, Hannah E; Satchell, Karla J F (2017) Efficacy of Ceftriaxone, Cefepime, Doxycycline, Ciprofloxacin, and Combination Therapy for Vibrio vulnificus Foodborne Septicemia. Antimicrob Agents Chemother 61:

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