Unveiling the Hidden Mechanism: How LuxS/AI-2 quorum sensing system drives antimicrobial resistance in Salmonella pullorum through activation of the efflux pump AcrAB-TolC

This is the authors' abstract. We don't add key points for this paper.

• The AMR of SP was enhanced by LuxS/AI-2 system by activating efflux pump AcrAB-TolC. • The LuxS protein didn't directly interact with the regulatory protein of efflux pump. • The signaling molecule AI-2 could bond with the SoxS protein via the hydrogen bond based on the the molecular docking. • AI-2 can activate efflux pump genes and soxS gene transcription to enhance the AMR. Understanding the antimicrobial resistance (AMR) mechanism of Salmonella pullorum (SP), which is widespread among yellow chickens in China, is crucial for reducing significant economic losses in the industry. In this study, we explored the AMR mechanism by which the LuxS/AI-2-mediated quorum sensing (QS) system regulates the AcrAB-TolC efflux pump in the SP. The results showed that the luxS gene and the signaling molecule AI-2 had no effect on the growth of the SP strains. However, the luxS gene knockout strain (SP129∆ luxS ) was sensitive to antimicrobials (ampicillin, methoxypyrimidine, sulfaisoxazole, trimethoprim/sulfamethoxazole and nalidixic acid), whereas SP129 was resistant. The SP129 strain was resistant to antimicrobials which had previously been proved to be sensitive to the antimicrobials following incubation with AI-2. Moreover, the expression levels of the soxS, acrA , and acrB genes, as well as the SoxS protein were significantly increased by knocking out the luxS gene or by incubating with Al-2. Crucially, there was no interaction between the LuxS protein and the SoxS or SoxR proteins. However, these two proteins were found to be bound to AI-2 via hydrogen bonds. In summary, AMR in SP isolates was enhanced by AI-2 through the promotion of the the expression of the soxS gene and the SoxS protein, activating the efflux pump. Exploring the AMR mechanism of the SP strain provides important baseline information for controlling outbreaks of yellow chicken salmonellosis.