LuxS/AI-2 system is involved in fluoroquinolones susceptibility in Streptococcus suis through overexpression of efflux pump SatAB

Increasing resistance to fluoroquinolones (FQs), such as norfloxacin and enrofloxacin, supports the need for the discovery of novel molecules and alternative approaches in antimicrobial therapy. Quorum sensing (QS) is promising target for next-generation anti-infective agents designed to address the evolving drug resistance bacterial pathogens. Given that the LuxS/autoinducer-2 (AI-2) quorum-sensing system regulates microbial grout behaviors, we hypothesized that this system influences the FQ susceptibility in Streptococcus suis. It was fowd that a luxS mutant (Delta luxS) of S. suis possesses an increased susceptibility to FQs compared to the wild type strain When grown in the presence of sub-MIC of antibiotics, the Delta luxS strain showed a significant decrease in growth rate and biofllm formation. These results suggest that the FQ resistance in S. suis could involve a signaling mechanism associated with the LuxS/AI-2 quorum-sensing system. HPLC (High Performance Liquid Chromatography) analyses showed a significant increase in the intracellular accumulation of enrofloxacin in the Delta luxS strain compared to the wild type strain. This increase was less pronounced in the presence of exogenous AI-2. Moreover, the expression of satA and satB genes was decreased in the Delta luxS strain. Exogenous AI-2 reversed the down-regulated gene expression observed in the Delta luxS strain. Our study brought strong evidence that the LuxS/AI-2 system in S. suis is involved in FQ susceptibility by regulating the efflux pump SatAB. LuxS is highly conserved among Gram-positive bacteria and may therefore represent a novel antimicrobial target for an alternative approach in antimicrobial therapy.