# Defining virulence factor functions using minimal pathogen genomes

> **NIH AI R01** · UT SOUTHWESTERN MEDICAL CENTER · 2026 · $596,318

## Abstract

Project Summary
Pathogenic bacteria have developed an array of strategies to undermine the host's defense mechanisms. In
the context of non-Typhoidal Salmonella Typhimurium, a notable strategy involves the confinement of a single
bacterium within a host vacuole called the Salmonella Containing Vacuole (SCV). This approach potentially
provides an evolutionary advantage: by ensuring one bacterium per SCV, the host must target each SCV
individually to eliminate the bacterial load, as opposed to confronting a vacuole harboring multiple bacteria
clustered together. This mechanism could potentially extend the time required to combat the infection.
Moreover, a single bacterium residing within an SCV exploits all accessible nutrients for replication and
division. Conversely, multiple bacteria clustered within a single vacuole may engage in nutrient competition.
Hence, understanding the fundamental mechanism of bacterial division in conjunction with vacuolar scission is
imperative for gaining deeper insights into the pathogenic strategies employed by Salmonella enterica. Prior to
this proposal we engineered a series of genetically minimal pathogenic strains that eliminates redundancy
within the complex SPI-2 effector gene repertoire of Salmonella enterica serovar Typhimurium. Using this
unique resource, here we will determine how a small network of SPI-2 T3SS effector proteins coordinate the
complex events involved in SCV membrane scission and bacterial division within the host cell. This includes
determining the location and host substrates of effector proteins at the SCV membrane using single cell
particle tracking and live cell imaging (Aim 1). We will also investigate the molecular mechanisms of individual
effector proteins that target a novel Rab-family GTPase defense system of the host (Aim 2). The resulting
cellular and biochemical theories will be tested in murine models of systemic disease that are designed to
evaluate effector protein functions at single cell resol

## Key facts

- **NIH application ID:** 11289809
- **Project number:** 1R01AI191274-01A1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Neal Mathew Alto
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** AI
- **Fiscal year:** 2026
- **Award amount:** $596,318
- **Award type:** 1
- **Project period:** 2026-02-10T00:00:00 → 2031-01-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11289809

## Citation

> US National Institutes of Health, RePORTER application 11289809, Defining virulence factor functions using minimal pathogen genomes (1R01AI191274-01A1). Retrieved via AI Analytics 2026-05-17 from https://api.ai-analytics.org/grant/nih/11289809. Licensed CC0.

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