# The Type 3 Secretion System Translocon Pore in Bacterial Pathogenesis

> **NIH NIH K22** · UNIVERSITY OF COLORADO DENVER · 2021 · $105,993

## Abstract

Abstract
Type 3 secretion systems (T3SSs) are expressed by approximately 30 different bacterial pathogens. They are
essential for the virulence of these organisms in humans, yet the mechanisms required for T3SS function are
incompletely understood. T3SSs form translocon pores in the membranes of mammalian cells. This pore is
required for the T3SS to translocate bacterial effector proteins across the mammalian membrane into the cell
cytosol. The molecular mechanisms required for the pore to support effector translocation are poorly
described. Shigella is a bacterial pathogen that requires a T3SS both to invade cells and then to spread into
adjacent cells. At invasion, the translocon pore interacts with mammalian intermediate filaments to support
T3SS function. In contrast, my preliminary data show Shigella spread into neighboring cells occurs
independent of intermediate filaments. These results suggest translocon pore function is different at discrete
stages of Shigella infection. The overall goals of this project are to investigate how the translocon pore
supports Shigella infection. I propose the following specific aims:
 Aim 1: To investigate the mechanisms by which interaction of IpaC with intermediate filaments leads to
docking.
 Aim 2: To test whether the IpaC coiled-coil domain participates in processes required for docking.
 Aim 3: To characterize the function of the translocon pore during cell-to-cell spread of Shigella.
During Phase 1 of this project, I will develop techniques and approaches to investigate the bacterial proteins
that comprise the Shigella flexneri translocon pore. Phase 1 of this award will be carried out in the laboratory of
Dr. Marcia Goldberg at Massachusetts General Hospital and Harvard Medical School. A career development
plan will be implemented emphasizing additional training and mentoring to prepare me for and during the
independent phase of this project. As an independent investigator, I will combine my previous training with new
skills to complete the remaining research objectives. This proposal is designed to allow me to achieve my long-
term research goals and to attain an independently funded faculty position that focuses on defining bacterial
virulence mechanisms and on exploiting these mechanisms to develop novel therapeutics to block infection.
!

## Key facts

- **NIH application ID:** 10190799
- **Project number:** 5K22AI137296-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Brian Russo
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $105,993
- **Award type:** 5
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10190799

## Citation

> US National Institutes of Health, RePORTER application 10190799, The Type 3 Secretion System Translocon Pore in Bacterial Pathogenesis (5K22AI137296-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10190799. Licensed CC0.

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