Characterization of agr-like Loci in Lactiplantibacillus plantarum and L. paraplantarum and Their Role in Quorum Sensing and Virulence Inhibition of Staphylococcus aureus

The pathogenicity of Staphylococcus aureus is largely regulated by the agr quorum sensing (QS) system encoded by agrBDCA, which coordinates virulence factor production through secretion and sensing of auto-inducing peptides (AIPs). agr-like systems are also present in coagulase-negative staphylococci, and several of these encode AIPs that inhibit S. aureus QS. In lactic acid bacteria, a similar locus was previously identified in Lactiplantibacillus plantarum WCSF1 termed lamBDCA. Here, we characterized the lamBDCA locus in L. plantarum LMG 13556 and L. paraplantarum CIRM-BIA 1870, and explored the effects on S. aureus QS. Notably, we found that co-cultivation with L. paraplantarum significantly inhibits S. aureus QS and hemolysin production, while less so for L. plantarum. The inhibition by L. paraplantarum was lost upon disruption of its lamBDCA locus, suggesting that the L. paraplantarum AIP mediates cross-species interference with S. aureus agr activation. Transcriptomic analysis revealed that lamBDCA in L. paraplantarum controls the expression of genes belonging to various functional categories, including stress response and metabolism. The latter includes genes encoding riboflavin (B2 vitamin) biosynthesis, which enabled the growth of the L. paraplantarum lamB mutant in the presence of roseoflavin, a toxic riboflavin analogue. Collectively, our results show that L. paraplantarum CIRM-BIA 1870 interferes with S. aureus virulence gene expression through QS suppression, and they implicate QS in the probiotic properties of L. paraplantarum.