The Distribution and Diversity of LuxI/LuxR Quorum Sensing Systems in Proteobacteria (Pseudomonadota)

Summary In Pseudomonadota (formerly Proteobacteria), the N -acyl homoserine lactone (AHL) quorum sensing (QS) system involves LuxI/LuxR modules, where LuxI synthesizes AHLs and LuxR-AHL regulates target gene expression. Despite extensive characterization in many bacterial species, the distribution, genomic organization, and taxonomic comprehensiveness of LuxI/R systems remains unexplored at scale. In this study, we present the first large-scale, genome-wide assessment of LuxI/R QS systems across over 30,000 publicly available genomes at chromosome-level and manually curated spanning 938 genera. Using pfam-based domain annotation, we mapped the distribution, occurrence, and copy number of LuxI/R homologs. LuxI/R systems were identified in ∼32% of surveyed genera, with notable enrichment in symbiotic and plant-associated taxa such as Rhizobium , Burkholderia , and Pseudomonas , and remarkable conservation in pathogenic taxa such as Yersinia , Aeromonas , and Acinetobacter . Conversely, entire genera, including Escherichia, Salmonella , and Klebsiella , among others, lacked LuxI/R systems across all sequenced strains, suggesting evolutionary loss, niche-specific signaling strategies, or reliance on alternative currently unknown communication systems. Our results also revealed genera with multiple, non-redundant and taxonomically not-related LuxI/R pairs per genome, indicating modular architectures and unpredictable events of horizontal gene transfer events and genetic arrangements. This study delineates the complex distribution and conservation patterns of LuxI/R circuits, providing a resource for future studies into AHL-mediated QS regulation, and microbial community interactions across diverse environments. Highlights LuxI/LuxR quorum-sensing systems show an uneven distribution across Pseudomonadota (formerly Proteobacteria) and evolved through expansion, conservation, and loss, reflecting diverse ecological strategies Among ∼31,815 high-quality Proteobacterial genomes, 6,400 (20.1%), corresponding to ∼303 genera (∼32%), encoded at least one complete LuxI/LuxR pair. Multiple, highly variable LuxI/R copies, up to seven per genome, reveal extensive horizontal gene transfer and mosaic evolutionary histories, especially in rhizobial and plant-associated taxa. Phylogenetic analyses distinguish genera with conserved QS architectures from those with fragmented, lineage-independent LuxI/R repertoires, possibly highlighting diverse ecological pressures shaping QS.