AI-2 quorum sensing system contributes fluoroquinolones resistance of Salmonella typhimurium by regulating metabolism

Abstract

The multidrug-resistant Salmonella is becoming major health threat due to inappropriate use of antibiotics. It is found that the metabolic changes contributed to bacterial drug resistance. AI-2 quorum sensing (QS) is involved in the regulation of bacterial metabolic activities. However, the role of AI-2 quorum sensing in the metabolic activities and drug resistance of Salmonella remain unclear. In this study, we determined the drug sensitivity of Salmonella typhimurium by 96-well plate and then determined the time-killing curve. Then, the regulation of AI-2 quorum sensing on Salmonella metabolic activity was analyzed by quantitative real‑time PCR and LC-MS metabonomics. The results showed that luxS mutant strain of Salmonella typhimurium lacking AI-2 quorum sensing was at least 4-fold less sensitive to killing by fluoroquinolone antibiotics. The decreased cell killing after the fluoroquinolones challenge was found to involve a low metabolic state presented by up-regulating anaerobic respiration, and LC-MS metabonomics analysis showed that the low metabolic state of luxS deletion strain might be related to the metabolism of amino acids such as leucine and valine. In conclusion, this study indicated that the deletion of luxS gene in Salmonella typhimurium mediated the tolerance to fluoroquinolones by affecting valine metabolism and up-regulating the anaerobic metabolism pathway.