# Establishment of an aqueous environment as a novel mechanism of bacterial pathogenesis

> **NIH NIH R01** · DUKE UNIVERSITY · 2024 · $394,211

## Abstract

Establishment of an aqueous environment as a novel mechanism of bacterial pathogenesis
PI: HE, Sheng Yang; Michigan State University
Project summary
Many bacterial pathogens of plants and mammals, including humans, use the highly conserved type III secretion system
(T3SS) to inject “effector proteins” into the host cell as an important paradigm of pathogenesis. The long-term goal of this
project is to characterize a newly discovered T3SS-mediated virulence strategy by which bacterial pathogens create an
aqueous extracellular environment in host tissues. In nature, many host-pathogen and host-microbiome interactions occur
in air-exposed/connected host organs/tissues (e.g., epidermis/skin and gas-exchange organs including respiratory systems
and plant leaves) in which water availability is limited and/or variable. Because microbes generally require a
moist/aqueous/mucous environment to survive and proliferate, it is not well understood whether microbes actively establish
an infection-conducive aqueous environment in host organs. In humans, malfunction of aquaporins has been associated with
infectious diseases, kidney malfunction and even cancer development and there is an emerging link between aquaporin-
mediated water transport and pathogenesis of enteropathogenic Escherichia coli. However, cause-effect relationships often
remain unclear. In the past 25 years, the Principal Investigator’s lab has used the model Arabidopsis thaliana – Pseudomonas
syringae interaction to discover and characterize T3SS-mediated bacterial infection mechanisms. By taking advantage of
the genetic tractability of Arabidopsis and a well-characterized T3SS effector repertoire in P. syringae, the PI’s lab recently
discovered a critical role of an aqueous environment in bacterial pathogenesis. In this application, three specific aims are
proposed to test the central hypothesis that, by altering (i) ARF-GEFMIN7-dependent vesicular traffic and (ii) phosphorylation
of aquaporins involved in regulating water transport across host plasma membrane, P. syringae disrupts water homeostasis
across the host plasma membrane, resulting in an aqueous extracellular environment as an important mechanism of
pathogenesis. Aim 1 will determine the role of ARF-GEFMIN7-associated host proteins in regulating vesicular traffic of
aquaporins and extracellular water. Aim 2 will investigate how P. syringae T3SS effector proteins target ARF-GEFMIN7-
associated vesicle traffic and aquaporins to induce an aqueous extracellular environment. Aim 3 will elucidate how
activation of host immunity prevents the virulence actions of P. syringae T3SS effectors as a novel dimension of the host
innate immune response. Contemporary methods in molecular genetics, cell biology, biochemistry and microbial
pathogenesis will be used in this study. Successful completion of this research will significantly advance our understanding
of a newly discovered bacterial virulence mechanism and its interplay with host innate immu...

## Key facts

- **NIH application ID:** 10908405
- **Project number:** 5R01AI155441-06
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** SHENG YANG HE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $394,211
- **Award type:** 5
- **Project period:** 2020-09-21 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10908405

## Citation

> US National Institutes of Health, RePORTER application 10908405, Establishment of an aqueous environment as a novel mechanism of bacterial pathogenesis (5R01AI155441-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10908405. Licensed CC0.

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