# Vibrio MARTX toxin effectors in signaling and pathogenesis

> **NIH NIH R37** · NORTHWESTERN UNIVERSITY · 2022 · $509,944

## Abstract

Project Summary
Bacteria
coordinated
autoprocessing
secreted
secreted
central portion of
 often coordinate secreted virulence factors to fine-tune he host response during infection. These
 events can include toxins counteracting or amplifying effects of another toxin. Multifunctional-
 repeats-in toxin (MARTX) toxins are large, secreted proteins that are a unique hybrids of
toxins and multi-effector delivery systems. Similar to many bacterial protein toxins, MARTX toxins are
from the bacteria and then form a pore in the host cell plasma membrane.
t
After translocation of the
the toxin, an autoprocessing cysteine protease domain is activated by binding inositol
hexakisphosphate. CPD-mediated autoproteolysis of the large polypeptide results in release of the “MARTX
effectors” to the cell cytosol, where they are free to move throughout the cell to access cellular targets and to
exert their toxic effects. There are over 100 different bacterial taxa that carry a MARTX toxin. Across the
different species, MARTX
They
together
stoichiometric
mechanism
together
repertoire
MARTX
could
this
virulence.
Vibrio
toxin
this
signal
 toxins carry up to 5 effector domains, selected from ten known effector domains.
have thus been called “cluster bombs”. An important feature of these toxins is hat all the effectors l inked
 in a single polypeptide are delivered simultaneously to the same cell at the same time, at equal
 ratio. While previous studies have employed a reductionist approach to determine the
of action of individual effector domains, little is known about how these ffector ctivities delivered
 may act in synergy to promote infection. Further, due to horizontal gene transfer, the toxin effector
can change frequently resulting in novel toxinotypes. Thus, the same effector domain in a different
 toxins may have context-dependent differences in cell signaling and contribution to virulenc. This
 impac the pathogenic potential o different clinical isolates, even within the same bacterial species. In
renewal study, we will focus on how different combinations of MARTX toxin effectors synergize to enhance
The study will focus on how the actin crosslinking MARTX effector found i both Vibrio cholerae and
 vulnificus can reprogram host cell signaling. We wil further ask how effectors co-delivered on the same
 then complement or override this signaling program to optimally promote virulence. We will then expand
 study into other MARTX toxins to explore if other combinations also show context-dependent impact on
coordination and pathogenesis.
t
,
e a
t f
n
l

## Key facts

- **NIH application ID:** 10375822
- **Project number:** 2R37AI092825-11
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Karla J F Satchell
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $509,944
- **Award type:** 2
- **Project period:** 2011-07-01 → 2026-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375822

## Citation

> US National Institutes of Health, RePORTER application 10375822, Vibrio MARTX toxin effectors in signaling and pathogenesis (2R37AI092825-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10375822. Licensed CC0.

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