# Enterobacterial infections as drivers of tauopathies

> **NIH NIH R56** · UNIVERSITY OF NEW MEXICO · 2020 · $378,750

## Abstract

PROJECT SUMMARY/ABSTRACT
Increasing evidence indicates a microbial etiology of Alzheimer’s disease (AD). One of the first signs of
neurodegeneration in humans is the loss of olfactory function. Importantly, the olfactory system constitutes a
direct portal of entry for microorganisms into the central nervous system (CNS). Yet, the role of neuro-invasive
microbes that exploit the olfactory route to cause neurodegenerative process remains unknown. Our long-term
goal is to understand the role of enterobacterial infections via the olfactory route in tauopathies to develop future
microbial interventions and early diagnostic tests. Shigellosis is a very common enterobacterial infection and
Shigella sonnei infection is the most common cause of diarrheal disease in the US. Preliminary data indicates
that S. sonnei infects the CNS of humans as well as the olfactory system and CNS of mice in models of human
tauopathy. The objective of this grant is to determine how shigellosis contributes to tau pathology. The central
hypothesis of this proposal is that S. sonnei can infect the nasal mucosa, penetrate the CNS and cause
neurodegeneration. Our specific aims will test the following hypotheses: S. sonnei nasal infection results in
cognitive impairment, tau pathology and neurodegeneration in an age-dependent manner (AIM #1); Shigella-
induced neurodegeneration occurs via protein tau (AIM #2); Shigella vaccines can slow down tau pathology
progression in mice (AIM #3). The proposed experiments will be performed using wild type mice as well as two
different mouse models of tauopathy, the hTau mouse model (expressing all six isoforms of non-mutant human
tau under the human MAPT regulatory element) and MAPT knock out mice. The significance of our proposed
studies is that it will advance our understanding on how shigellosis, a very common enterobacterial pathogen in
the U.S can cause neurodegeneration in the CNS. This proposal will inform aspects of microbial interventions
such as vaccination to slow down neurodegeneration. Our results may also have diagnostic implications since
sequencing of the nasal microbiome of tauopathy patients may become a critical early diagnostic test in the
clinic.

## Key facts

- **NIH application ID:** 10236817
- **Project number:** 1R56AG067469-01
- **Recipient organization:** UNIVERSITY OF NEW MEXICO
- **Principal Investigator:** Irene Salinas
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $378,750
- **Award type:** 1
- **Project period:** 2020-09-30 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10236817

## Citation

> US National Institutes of Health, RePORTER application 10236817, Enterobacterial infections as drivers of tauopathies (1R56AG067469-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10236817. Licensed CC0.

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