# IRON UPTAKE AS A VIRULENCE FACTOR IN PATHOGENIC VIBRIOS

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 1991 · $165,641

## Abstract

The long term objective of the proposed research is the detailed analysis
of a virulence associated property, plasmid-mediated iron uptake, which
plays an important role in the pathogenesis of many invasive septicemic
diseases of man and domestic animals. Our model system is the fish pathogen
Vibrio anguillarum which causes a terminal hemorrhagic septicemia. This
bacterium possesses a plasmid-mediated iron uptake system that is an
important component of its virulence repertoire. The features of this
plasmid-mediated virulence determinant makes it a very attractive model to
study host-bacterial interactions. In the past granting period we have
characterized the essential components of this system: the siderophore
anguibactin; the transport proteins OM2 and P40, and regulatory elements
controlling their biosynthesis. The specific mechanisms by which these
components regulate the process of iron uptake, and thus virulence, in V.
anguillarum will be further elucidated by the proposed investigation. The
specific aims to achieve these objectives are: 1) To identify the genetic
determinants and their encoded polypeptides involved in the biosynthesis of
the siderophore anguibactin. We will use a combination of genetic and
physical methods to dissect the biosynthetic pathway of anguibactin. 2) To
characterize the mechanism of transport of iron into the cell cytosol and
investigation of the role played by P40, OM2 and the products of ORFs 1 and
2 also encoded in the iron transport region. 3) To define the nature of the
positive regulation of the expression of iron-uptake genes in V.
anguillarum by the transcriptional regulators AngR and TAF. 4) to define
the nature of the negative regulation by iron of the expression of iron
transport genes. We have identified an antisense RNA encoded in the P40-OM2
intergenic region that is induced under iron-rich conditions, concomitant
with a decrease in the synthesis of the P40 and OM2 mRNAs. Our evidence
indicates that this antisense RNA may play a role in the iron regulation of
the expression of the P40 and OM2 iron transport genes in V.anguillarum. We
will determine whether this is the central mechanism of repression of iron
transport in this bacterium or whether it is part of a more complex
regulatory circuit that may also include Fur-like elements. In summary, the
molecular studies of this plasmid-mediated iron-uptake system should
provide useful information in both the basic aspects of plasmid-mediated
iron uptake and its role as a bacterial virulence factor.

## Key facts

- **NIH application ID:** 3128436
- **Project number:** 5R01AI019018-10
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **SAM.gov UEI:** NPSNT86JKN51
- **Principal Investigator:** JORGE H CROSA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $165,641
- **Award type:** 5
- **Project period:** 1982-04-01 → 1995-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3128436

## Citation

> US National Institutes of Health, RePORTER application 3128436, IRON UPTAKE AS A VIRULENCE FACTOR IN PATHOGENIC VIBRIOS (5R01AI019018-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3128436. Licensed CC0.

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