# Understanding the molecular mechanisms and biological functions of a novel bleach-sensing bacterial receptor in shaping host-associated bacterial populations in response to host inflammation

> **NIH NIH K99** · UNIVERSITY OF OREGON · 2020 · $117,420

## Abstract

PROJECT SUMMARY/ABSTRACT
A large body of research has elucidated the role of bleach (HOCl) as a potent antimicrobial produced by the
immune system through neutrophil myeloperoxidase, but new findings have provided intriguing instances in
which this paradigm is challenged, and some important human bacterial pathogens such as Salmonella
Typhimurium and Helicobacter pylori have been shown to actually be attracted to inflamed tissue—where HOCl
can reach millimolar concentrations—and can exploit host inflammation processes to colonize and establish
persistent infections. The molecular basis for how these bacteria can use motility and chemotaxis to respond to
HOCl and reaction products is mostly unknown, and represents an important new direction for infectious disease
research with the potential to provide many insights into how pathogenic and commensal bacteria colonize and
persist in animal hosts to cause disease. The broad and long-term objective of this project is to learn how
host-associated bacteria navigate the inflammation and redox landscape of the gut, which has implications for
many human infectious diseases, especially those involving bacterial-promoted chronic inflammation such as
stomach cancer, ulcerative colitis, and inflammatory bowel diseases. The key focus of this project is to advance
understanding of how host-associated bacteria sense and respond to inflammation by investigating a novel
bleach-sensing regulatory module referred to as chemoreceptor zinc-binding (CZB) domains that are conserved
broadly in commensal and pathogenic bacteria. Specific Aim 1 will use a reductionist in vitro approach to test if
CZB domains function through a conserved mechanism by analyzing residue conformation patterns and
determining the reactivity with HOCl of representative CZB proteins from H. pylori, S. Typhimurium, and E. coli.
Specific Aim 2 will perform the first tests of the biological roles of CZB domains in bacterial infections with a
novel ELISA chemotaxis assay and infections in zebrafish and mouse model organisms.
 Important for the Career Development of Dr. Arden Perkins, this project will provide him comprehensive new
training in using animal models, which he has never done, as well as expertise in microscopy and live imaging,
and genetic engineering of bacteria. This training will build on Dr. Perkins’ prior experience in protein
crystallography, drug discovery, and redox biology to make him a competent investigator at the interface of in
vitro and in vivo work, and enable him to pursue investigations into the functions of key proteins involved in
bacterial infections at the molecular and biological levels. Dr. Perkins will be trained at University of Oregon in
the zebrafish system, a high throughput model in which he will study bacterial dynamics and responses to
neutrophils in situ, and collaborators Dr. Manuel Amieva at Stanford and Dr. Andreas Baumler at UC Davis will
provide expert guidance and support for extending these studies to...

## Key facts

- **NIH application ID:** 9871624
- **Project number:** 1K99AI148587-01
- **Recipient organization:** UNIVERSITY OF OREGON
- **Principal Investigator:** Arden Baylink
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $117,420
- **Award type:** 1
- **Project period:** 2020-07-16 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9871624

## Citation

> US National Institutes of Health, RePORTER application 9871624, Understanding the molecular mechanisms and biological functions of a novel bleach-sensing bacterial receptor in shaping host-associated bacterial populations in response to host inflammation (1K99AI148587-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9871624. Licensed CC0.

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