# Sortase A regulates cell wall integrity, quorum sensing, and biofilm formation to modulate adhesion properties in Lactiplantibacillus plantarum C8

## TL;DR

This study shows that Sortase A in Lactiplantibacillus plantarum helps the bacteria stick to surfaces, form biofilms, and adapt to the gut environment, which is important for its probiotic benefits.

## Contribution

The study reveals Sortase A as a master regulator linking cell wall integrity, quorum sensing, and adhesion in a probiotic bacterium.

## Key findings

- srtA deletion disrupts pathways for environmental adaptation and biofilm formation.
- srtA deletion leads to impaired cell wall integrity and reduced adhesion in L. plantarum C8.
- srtA integrates QS-regulated biofilm dynamics and surface protein function via metabolic pathways.

## Abstract

Lactiplantibacillus plantarum, a ubiquitous probiotic in fermented foods and the human gut, relies on gastrointestinal tract colonization for its health-promoting functions. Central to this colonization is Sortase A (SrtA), a transpeptidase that anchors LPXTG motif-containing proteins to the cell wall peptidoglycan layer. This study investigates the srtA-mediated regulatory axis linking cell wall integrity, biofilm formation, and quorum sensing (QS) to adhesion properties in L. plantarum C8 (CGMCC No. 30504). Gene Ontology (GO)–KEGG enrichment analysis reveals that srtA deletion disrupts pathways critical for environmental adaptation, including two-component signal transduction and AI-2-dependent QS. Furthermore, the results of differential gene expression analysis indicate that srtA deletion is associated with the downregulation of genes involved in pyruvate metabolism, amino sugar/nucleotide sugar metabolism (essential for exopolysaccharide biosynthesis), and cell wall-associated signaling cascades, processes linked to adhesion and colonization. The molecular-level alterations were consistent with the observed phenotypic changes, including impaired cell wall integrity, reduced adhesion, and diminished biofilm-forming capacity. These results establish a mechanistic connection between srtA-directed cell wall anchoring, QS-regulated biofilm dynamics, and probiotic adhesion efficacy in L. plantarum.

Gastrointestinal tract colonization is the foundation of probiotic efficacy, enabling Lactiplantibacillus plantarum to modulate the gut microbiota, reinforce intestinal barriers, and confer health benefits. Sortase A (SrtA) is central to this process, covalently anchoring LPXTG-containing surface proteins that mediate adhesion, biofilm formation, and immune modulation. While srtA’s role in pathogenic Gram-positive bacteria is well documented, its regulatory functions in non-pathogenic probiotic strains remain largely unexplored—especially regarding its integration with quorum sensing (QS) and environmental adaptation pathways. This study dissects the srtA-mediated molecular network in L. plantarum C8, revealing srtA as a master regulator integrating cell wall integrity, QS-regulated biofilm dynamics, and surface protein function via pathways including pyruvate and amino sugar/nucleotide sugar metabolism. These insights provide a mechanistic foundation for engineering probiotic strains with enhanced adhesion, colonization, and persistence and offer a scientific basis for developing precision-targeted functional foods and therapeutics.