# Small host GTPases: Direct targets of Vibrio vulnificus MARTX toxin effectors

> **NIH NIH K99** · NORTHWESTERN UNIVERSITY · 2021 · $98,524

## Abstract

Project Summary/Abstract
Gastrointestinal and wound infections caused by the Gram-negative bacterium Vibrio vulnificus (Vv) can be
exceptionally life-threatening resulting in death in approximately 50% of cases. These infections progress within
days and must be identified and treated quickly to decrease mortality and morbidity. While antibiotics are used
to treat Vv infections, they are often ineffective as the disease progresses rapidly, especially in
immunocompromised individuals. This disease is of particular concern now as the incidence of the disease is
increasing due to climate change. The Multifunctional Autoprocessing Repeats in Toxin (MARTX) toxin is a large
protein toxin that is secreted by Vv and is essential to cause infections. The MARTX toxin functions to deliver up
to five different toxic effectors as a single bolus directly into the eukaryotic host cytoplasm. There are ten known
unique effectors, and each is capable of causing cytotoxic effects. Determining the mechanism by which the
effectors encoded within the MARTX toxin function will reveal a novel mechanisms related to bacterial toxin
function that could impact our understanding of host-microbe interactions across many diverse systems. The
Makes Caterpillars Floppy-like (MCF) toxin is the most common Vv MARTX effector. MCF is linked to Golgi
dispersion, inhibition of cell proliferation, and apoptosis. In preliminary studies, MCF is observed to be stimulated
to autoprocess via binding to ADP-ribosylation factors resulting in its absolute release as an individual effector
domain within the host cell and activation. However, how MCF functions within the eukaryotic host once
individually released and activated that results in its toxicity is unclear. The goal of this proposal is to investigate
the hypothesis that, once activated, MCF moves on to bind and target another class of small GTPases, Rabs,
resulting in a disruption of proper cell functions. To test this hypothesis, we will determine: 1) Which subset of
Rabs are the target of MCF; 2) How MCF gains access to these Rabs; 3) How this interaction alters proper Rab
functioning and localization; 4) The manner in which these two proteins interact; and 5) The function of the
different domains of MCF. In addition, these studies will involve training to utilize novel techniques and concepts.
The results from this work have the potential to develop into several independent research projects. The
proposed fellowship will involve collaborations, which are facilitated and encouraged in the Department of
Microbiology-Immunology at Northwestern.

## Key facts

- **NIH application ID:** 10283852
- **Project number:** 1K99AI167819-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Alfa Herrera
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $98,524
- **Award type:** 1
- **Project period:** 2021-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10283852

## Citation

> US National Institutes of Health, RePORTER application 10283852, Small host GTPases: Direct targets of Vibrio vulnificus MARTX toxin effectors (1K99AI167819-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10283852. Licensed CC0.

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