# IRON TRANSPORT AND VIRULENCE IN SHIGELLA

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 1993 · $173,036

## Abstract

Most organisms have an absolute requirement for iron.  The scarcity of
free iron in vertebrate hosts may limit infection and invasion by
pathogenic microorganisms.  Thus, competition for this element plays a
pivotal role in host-bacterial interactions.  Reduced levels of available
iron in the host not only limit bacterial growth but also act as a
regulatory signal to induce synthesis of iron acquisition systems,
certain toxins, and other proteins associated with virulence.  Thus iron
is one of a number of environmental stimuli to which pathogens respond.

The broad objectives of this project are to (A) study the structure and
regulation of bacterial iron transport genes, (B) determine the mechanism
of iron acquisition in vivo, and (C) study the genes and gene products
which are differentially expressed in the host and determine the signals
which, in addition to iron, regulate their expression.  The model system
for these studies is the enteric pathogen Shigella flexneri.  This
pathogen causes disease by invading and multiplying within intestinal
epithelial cells, and thus is a model for studying invasive,
intracellular pathogens.  S. flexneri is readily amenable to genetic and
biochemical analysis, and tissue culture can be used to study the
interaction of these bacteria with host cells.

The specific goals of this proposal are to 1) determine the mechanism by
which Shigella utilize heme as a sole source of iron, 2) determine the
role of the heme-iron transport system in virulence, and 3) measure the
expression of iron transport and other virulence-associated genes within
host cells.

Genetic and biochemical approaches will be used to study heme transport.
The genes encoding the system will be cloned, and mutants will be
isolated to study gene function and regulation.  Those mutants defective
in binding or transport of heme will also be tested for invasion and
intracellular multiplication in tissue culture systems.  In addition to
in vitro analysis, techniques have been developed to measure protein
expression by S. flexneri invading or multiplying within host cells.
This provides a tool for determining expression of virulence factors in
vivo and, in the long term, will be a useful technique in design and
analysis of potential vaccine strains.

## Key facts

- **NIH application ID:** 3126907
- **Project number:** 2R01AI016935-09A4
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **SAM.gov UEI:** V6AFQPN18437
- **Principal Investigator:** Shelley M. Payne
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $173,036
- **Award type:** 2
- **Project period:** 1980-09-30 → 1998-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126907

## Citation

> US National Institutes of Health, RePORTER application 3126907, IRON TRANSPORT AND VIRULENCE IN SHIGELLA (2R01AI016935-09A4). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126907. Licensed CC0.

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