# Host iron and Yersinia pathogenesis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2020 · $491,921

## Abstract

The majority of bacterial pathogens require iron as an essential nutrient and mammalian hosts have evolved a
number of mechanisms to sequester iron and limit the growth of invading microbes. However, bacteria have, in
turn, evolved a myriad of iron uptake strategies as well as regulatory proteins that sense iron levels to control
expression of iron acquisition systems and other genes critical for virulence. Iron is an important factor in the
pathogenesis of the plague agent Yersinia pestis and the enteropathogens Y. enterocolitica and Y.
pseudotuberculosis. We recently showed that Y. pseudotuberculosis uses an iron-sulfur cluster coordinating
transcription factor called IscR to drive expression of its major virulence factor, the Ysc type III secretion
system (T3SS), and that IscR is required for proper expression of a number of other metabolic and virulence
genes. Our preliminary data show that IscR is required for Y. pseudotuberculosis virulence and for survival in
blood. As IscR is a global transcriptional regulator, it is critical to determine precisely which IscR-regulated
pathways are important for pathogen growth and survival in vivo. To address this, in Aim 1, we will determine
the IscR regulon in Y. pseudotuberculosis, how it is influenced by iron levels, and assess its conservation in Y.
pestis and Y. enterocolitica. In addition, in Aim 2, we will test how IscR control of the Ysc T3SS impacts Y.
pseudotuberculosis virulence in normal and iron overloaded mice. Lastly, in Aim 3, we will determine how IscR
enables Y. pseudotuberculosis survival in blood and how this influences disseminated infection. At the
conclusion of this study, we will have established the pathways controlled by IscR in Yersinia and determined
how they contribute to pathogenesis. This work will help to elucidate the ways in which pathogens sense their
environment to optimize virulence factor utilization during infection.

## Key facts

- **NIH application ID:** 9913985
- **Project number:** 5R01AI119082-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA CRUZ
- **Principal Investigator:** Victoria Auerbuch Stone
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $491,921
- **Award type:** 5
- **Project period:** 2016-05-10 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9913985

## Citation

> US National Institutes of Health, RePORTER application 9913985, Host iron and Yersinia pathogenesis (5R01AI119082-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9913985. Licensed CC0.

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