# Serine-rich repeat proteins in evolution of Lactobacillus-host specificity

> **NIH NIH R21** · CARNEGIE INSTITUTION OF WASHINGTON, D.C. · 2023 · $242,295

## Abstract

Abstract
Probiotic lactobacilli colonize mucosae and benefit human health by preventing infections,
reducing cancer risk, and improving metabolism. Among the lactobacilli, Lactobacillus plantarum
is one of the most widely studied probiotics. Lactobacilli use surface molecules called adhesins
to form physical associations with host tissues, and serine-rich repeat proteins (SRRPs) are one
specific class of adhesin used by probiotics and pathogens alike within in the Lactobacillaceae.
A key gap in our knowledge is how these proteins evolve specificity for their colonization site
within the host. This proposal investigates the hypothesis that cell-cell competition inside the
host creates an evolutionary selection pressure on SRRP genes to maximize bacterial cell
fitness inside the host. We investigate the first SRRP genes discovered in L. plantarum, which
we found to be necessary for colonization of a specific physical niche in the host digestive tract.
The proposal will examine evolution and specialization of the SRRP genes as well as the
functions of specific subdomains of the protein for their role in binding host mucus vs forming a
biofilm, vs promoting bacterial growth within the niche by enzymatically liberating host glycans.
We will use in vivo assays to connect the molecular properties of the SRRPs to cellular fitness
in the host. These assays include imaging the bacteria at single cell resolution inside the guts of
living animals to visualize the cell-cell competition directly. Success in this work could develop
an unparalleled model system to study the evolution of colonization specificity. Due to the wide
conservation of SRRPs in binding host mucus, this model may reveal conserved genetic
mechanisms that can be applied to develop better probiotics for humans and combat mucosal
pathogens.

## Key facts

- **NIH application ID:** 10573683
- **Project number:** 1R21AI173779-01
- **Recipient organization:** CARNEGIE INSTITUTION OF WASHINGTON, D.C.
- **Principal Investigator:** William Basil Ludington
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $242,295
- **Award type:** 1
- **Project period:** 2023-03-13 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10573683

## Citation

> US National Institutes of Health, RePORTER application 10573683, Serine-rich repeat proteins in evolution of Lactobacillus-host specificity (1R21AI173779-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10573683. Licensed CC0.

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