# Autoinducer 2 as a universal language in microbial consortia: decoding molecular mechanisms, ecological impacts, and application

**Authors:** Shuyu Guo, Bingyong Mao, Xin Tang, Qiuxiang Zhang, Jianxin Zhao, Wei Chen, Shumao Cui

PMC · DOI: 10.1080/19490976.2026.2615494 · Gut Microbes · 2026-01-23

## TL;DR

This review explores AI-2, a microbial signaling molecule, and its role in communication, community dynamics, and applications in health, agriculture, and environmental sustainability.

## Contribution

The paper systematically synthesizes AI-2's structural dynamics, receptor diversity, and ecological impacts, charting a roadmap for its application in microbial communication.

## Key findings

- AI-2 exhibits dual structural dynamics and mediates bacterial crosstalk through diverse receptors like LuxP and LsrB.
- AI-2 regulates metabolic flux and enables coordinated bacterial responses to environmental changes.
- Factors like strain specificity, nutrition, and environmental stress influence AI-2 production and signaling.

## Abstract

In natural and engineered ecosystems, diverse species interact in complex ways to form highly efficient microecologies. One key orchestrator of these interactions is autoinducer-2 (AI-2), a signaling molecule that plays a crucial role in microbial community assembly, metabolic flux, and resilience to environmental disturbances. This review provides the systematic synthesis of AI-2’s dual structural dynamics (S-THMF-borate/R-THMF interconversion) and its context-dependent roles in mediating bacterial crosstalk. It also reveals the receptor diversity (such as LuxP and LsrB) of AI-2 in bacterial kingdom and the signal transduction mechanism. Systematically elaborated on AI-2’s regulation of cellular metabolic flux and its ability to autonomously exhibit a series of coordinated behaviors in response to environmental changes. The review explores the ramifications of AI-2 on bacterial community interactions in synthetic biology and natural ecosystems. The wide application of AI-2-mediated interspecific communication in various fields including host health, agriculture, industry and environmental ecology has also been widely discussed. Factors influencing AI-2 production are thoroughly examined, including internal factors such as strain specificity, cell density, growth form and the phenotypic heterogeneity. Additionally, external biological factors (such as nutritional status and environmental stress) and abiotic factors (aggregation, diffusion, and flow) are discussed in detail. By examining knowledge gaps in AI-2-mediated spatial heterogeneity and multi-QS system coordination, this work charts a roadmap for harnessing microbial communication in chemical engineering and environmental sustainability.

## Linked entities

- **Proteins:** lsrB (autoinducer 2-binding protein)
- **Chemicals:** AI-2 (PubChem CID 446576), S-THMF-borate (PubChem CID 446576), R-THMF (PubChem CID 448719)

## Full-text entities

- **Genes:** enolase [NCBI Gene 20493233], aldehyde dehydrogenase [NCBI Gene 17035736]
- **Diseases:** nutrient deficiencies (MESH:D007153), lung inflammation (MESH:D011014), inflammation (MESH:D007249), acute lung injury (MESH:D055371), dysbiosis (MESH:D064806), cystic fibrosis (MESH:D003550), bacterial and parasitic infections (MESH:D010272), NEC (MESH:D020345), copper toxicity (MESH:C535468), tumor (MESH:D009369), AMC (MESH:C565394), infection (MESH:D007239)
- **Chemicals:** Hydrogen peroxide (MESH:D006861), water (MESH:D014867), CLA (MESH:D044243), aldehydes (MESH:D000447), alcohols (MESH:D000438), benzaldehyde (MESH:C032175), bile acids (MESH:D001647), PL-1 (MESH:D000077543), curcumin (MESH:D003474), S-THMF-borate (MESH:C531128), methane (MESH:D008697), benzoic acid (MESH:D019817), Hcy (MESH:D006710), oxygen (MESH:D010100), carbohydrate (MESH:D002241), c-di-GMP (MESH:C062025), D-ribose (MESH:D012266), heavy metal (MESH:D019216), phenyllactic acid (MESH:C017648), TCS (MESH:D013667), 4,5-dihydroxy-2,3-pentanedione (MESH:C493138), ethanol (MESH:D000431), carbon (MESH:D002244), Boron (MESH:D001895), ketones (MESH:D007659), glycylleucine (MESH:C015905), galactose (MESH:D005690), iron (MESH:D007501), AI-2 (MESH:C091088), Atrazine (MESH:D001280), short-chain fatty acids (MESH:D005232), 2,5-dimethyl-4-hydroxy-3(2 H)-furanone (MESH:C058427), L-cysteine (MESH:D003545), (2S,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran-borate (MESH:C525623), furan (MESH:C039281), methionine (MESH:D008715), (2S,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuryl borate (-), 10-undecenoic acid (MESH:C538763), amino acid (MESH:D000596), S-adenosylhomocysteine (MESH:D012435), borate (MESH:D001881), AHLs (MESH:D054742), CAI-1 (MESH:C525620), nitrogen (MESH:D009584), S-adenosylmethionine (MESH:D012436)
- **Species:** Lactiplantibacillus plantarum (species) [taxon 1590], Metaphire sieboldi (earthworm, species) [taxon 506672], Porphyromonas gingivalis (species) [taxon 837], Rhizobium (genus) [taxon 379], gut metagenome (species) [taxon 749906], Bacillus velezensis SQR9 (strain) [taxon 1423138], Klebsiella michiganensis (species) [taxon 1134687], Penicillium (genus) [taxon 5073], Homo sapiens (human, species) [taxon 9606], Pseudomonas aeruginosa (species) [taxon 287], Candida albicans (species) [taxon 5476], Clostridioides difficile (species) [taxon 1496], Lysobacter (genus) [taxon 68], Streptococcus mitis (species) [taxon 28037], Lactiplantibacillus plantarum subsp. plantarum (subspecies) [taxon 337330], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Bifidobacterium longum (species) [taxon 216816], Citrobacter rodentium (species) [taxon 67825], Mus musculus (house mouse, species) [taxon 10090], Bacteroides fragilis (species) [taxon 817], Lacticaseibacillus rhamnosus (species) [taxon 47715], Bacillus cereus (species) [taxon 1396], Ralstonia (genus) [taxon 48736], Salmonella enterica subsp. enterica serovar Typhimurium (no rank) [taxon 90371], Agrobacterium (genus) [taxon 357], Escherichia coli (E. coli, species) [taxon 562], Streptococcus gordonii (species) [taxon 1302], Shewanella putrefaciens (species) [taxon 24], Shewanella baltica (species) [taxon 62322], Vibrio cholerae (species) [taxon 666], Cucumis sativus (cucumber, species) [taxon 3659], Aggregatibacter actinomycetemcomitans (species) [taxon 714], Vibrio parahaemolyticus (species) [taxon 670], Leptospira sp. AB (species) [taxon 103236], Prevotella (genus) [taxon 838], Bacillus amyloliquefaciens (species) [taxon 1390], Lactobacillus gasseri (species) [taxon 1596], Escherichia coli O157:H7 (no rank) [taxon 83334], Microbacterium (genus) [taxon 33882], Streptococcus pneumoniae (species) [taxon 1313], Acinetobacter sp. (species) [taxon 472], Pyrus communis (pear, species) [taxon 23211], Streptococcus suis (species) [taxon 1307], Pantoea sp. (species) [taxon 69393], Vibrio (genus) [taxon 662], Pseudomonas putida (species) [taxon 303], Burkholderia cepacia (species) [taxon 292], Nitratidesulfovibrio vulgaris str. Hildenborough (strain) [taxon 882], Eriobotrya japonica (loquat, species) [taxon 32224], Pichia sp. (species) [taxon 4925], Enterococcus faecalis (species) [taxon 1351], Fructilactobacillus sanfranciscensis (species) [taxon 1625], Streptococcus mutans (species) [taxon 1309], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Bacillus subtilis (species) [taxon 1423], Paenarthrobacter sp. (species) [taxon 1931993], Lacticaseibacillus casei (species) [taxon 1582], Helicobacter pylori (species) [taxon 210], Bacteroides ovatus (species) [taxon 28116], Vibrio harveyi (species) [taxon 669]
- **Cell lines:** CT-26 — Mus musculus (Mouse), Mouse colon adenocarcinoma, Cancer cell line (CVCL_7254), DKY-1 — Mus musculus (Mouse), Hybridoma (CVCL_C7RB)

## Full text

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## Figures

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## References

183 references — full list in the complete paper: https://tomesphere.com/paper/PMC12834153/full.md

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Source: https://tomesphere.com/paper/PMC12834153