# The Role of TamAB in Salmonella Pathogenesis

> **NIH NIH R21** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2021 · $187,044

## Abstract

ABSTRACT
 Salmonella Typhimurium is a major food-borne pathogen that propagates within macrophages,
leading to life-threatening disease. The long-term objectives of our research are to understand the
molecular mechanisms by which Salmonella circumvents the host immune system to cause disease.
The outer membrane of the bacterium is the interface with the immune system. Outer membrane beta-
barrel proteins are normally assembled by the Bam complex. A homolog of Bam, the TamAB
translocation module is highly conserved in the Gammaproteobacteria. Originally proposed as a system
for assembly of a subset of beta-barrel proteins, the so-called autotransporter proteins, the actual
function of TamAB is unknown. We have discovered that tamAB is a previously unrecognized member
of the PhoPQ regulon and is induced when Salmonella is replicating in macrophages, suggesting that
this system is important for virulence. Indeed, our preliminary data strongly support our primary
hypothesis that TamAB is induced to assist Bam function under the stressful conditions in the
phagosome. Our secondary hypothesis is that TamAB is required for proper assembly of
particular proteins in the outer membrane under the conditions in the phagosome, and that
decreases or loss of these proteins attenuate Salmonella virulence. In Aim 1, we will determine
outer membrane composition using mass spectrometry, and monitor expression of envelope stress
response systems, to determine the biochemical and regulatory effects caused by loss of TamAB,
thereby identifying proteins that directly or indirectly require TamAB for proper assembly. We will also
isolate mutations that suppress in vitro defects in outer membrane permeability conferred or
exacerbated by loss of TamAB. In Aim 2, we will characterize identified loci and their role in
macrophage survival and virulence. The overall role of the identified factors in macrophage survival
will be revealed by genetic interactions with tamAB. Understanding the roles of TamAB will inform us
about the conditions in the phagosome leading to outer membrane assembly stress and the
mechanisms used by Salmonella to combat them. Identifying the specific proteins affected by loss of
TamAB also identifies additional virulence factors critical for Salmonella pathogenesis.

## Key facts

- **NIH application ID:** 10287293
- **Project number:** 1R21AI163687-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** JAMES M. SLAUCH
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $187,044
- **Award type:** 1
- **Project period:** 2021-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10287293

## Citation

> US National Institutes of Health, RePORTER application 10287293, The Role of TamAB in Salmonella Pathogenesis (1R21AI163687-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10287293. Licensed CC0.

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