# Determine host surface interactions of MARTX toxin of foodborne Vibrio vulnificus

> **NIH NIH F31** · NORTHWESTERN UNIVERSITY · 2022 · $41,965

## Abstract

Project Summary/Abstract
The marine pathogen Vibrio vulnificus is a highly lethal Gram-negative bacteria inhabiting coastal waters. It
causes intestinal infections via consumption of raw seafood and wound infections via open wounds. The infection
progresses rapidly to septicemia with high fatality rates. This bacterium exerts the highest economic cost of any
seafood-related disease. As multi-antibiotic resistant isolates have been detected and infection incidence is
climbing due to climate change, studies elucidating the pathogenic mechanisms of V. vulnificus are increasingly
important to support novel therapeutic development. The Multifunctional-Autoprocessing Repeats-in-Toxin
(MARTX) toxin has been shown in animal studies to be the primary virulence factor of V. vulnificus associated
with death. The goal of the proposed project is to determine pathogenic mechanisms of MARTX at host cell
surfaces that are necessary for intoxication. Addressing this question could provide critical information toward
design of antibodies that would function to block MARTX from binding to its targeted cells. This goal is particularly
pertinent to the NIAID given the institute's mission to support research to better understand, treat, and prevent
infectious diseases. Specifically, the first aim will determine host receptors for the V. vulnificus MARTXVv toxin.
Our preliminary data using an unbiased Genome-wide CRISPR-Cas9 Screening approach identified a host cell
membrane protein kinase as the most promising receptor candidate. In this aim, we will use a combination of
genetic manipulation, in vitro cellular assays and FRET based flow cytometry to validate the role of this kinase
as a MARTXVv receptor. The second aim will determine which regions of MARTXVv can bind to the cellular surface
based on previous studies on MARTXVv fragments, using techniques including protein purification, cell-based
binding assays and fluorescence microscopy. Collective, these data will define the host receptor and receptor
binding domain of the toxin revealing critical interactions between the toxin and host at cellular surface, the first
step of MARTXVv intoxication. Completion of the proposed work will provide training opportunities required to
support the long-term career goal of becoming a principal investigator studying bacterial toxins. Specifically, the
training will include 1) developing expertise in studying toxin functions in the host cell system, 2) developing
experimental techniques in genetic screens, immunofluorescence, and protein biochemistry and 3) developing
general skills required for academic independent researchers such as grant writing and scientific communication.
Northwestern University Feinberg School of Medicine provides an outstanding training environment for
accomplishing these goals. The sponsor Dr. Karla Satchell is an expert in bacterial toxins and protein structure.
The trainee will gain a depth of knowledge in studying toxin biology by having weekly meet...

## Key facts

- **NIH application ID:** 10537885
- **Project number:** 1F31AI172382-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Jiexi Chen
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $41,965
- **Award type:** 1
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10537885

## Citation

> US National Institutes of Health, RePORTER application 10537885, Determine host surface interactions of MARTX toxin of foodborne Vibrio vulnificus (1F31AI172382-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10537885. Licensed CC0.

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