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bioRxiv · 10.1101/2025.02.05.636741

Dietary quorum quenching AHL lactonase impairs the adaptation of commensal bacterium to host innate immunity

Xia, R.·Yao, Y.·Meng, D.·Zhao, Y.·Xu, S.·Jin, Y.·Zhang, Z.·Yang, Y.·Ran, C.·Zhou, Z.
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Abstract

Quorum sensing (QS) is the communication system of bacteria that depends on QS signals. Quorum quenching (QQ) enzymes degrade QS signals and are promising alternatives of antibiotics to treat bacterial infections. Here, we found that dietary QQ N-acyl homoserine (AHL) lactonase led to microbiota dysbiosis in zebrafish, with reduction of Aeromonas and enrichment of Plesiomonas. Through gnotobiotic zebrafish colonized with a minimal microbiota, we found that QQ-mediated microbial alteration relies on host Myd88 signaling and neutrophil elastase. Mechanistically, quorum quenching increased the susceptibility of commensal Aeromonas to host neutrophil elastase by impairing bacterial lateral flagellar system, leading to reduced colonization of Aeromonas and subsequent enrichment of Plesiomonas due to ecological competition of the two species. Together, we found that dietary QQ lactonase led to microbiota alteration by impairing the adaptation of commensal Aeromonas to host innate immunity, which provided novel insight in the role of quorum sensing in host-microbiota interaction.

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Xia, R., Yao, Y., Meng, D., Zhao, Y., Xu, S., Jin, Y., Zhang, Z., Yang, Y., Ran, C., Zhou, Z.. 2025-02-06. Dietary quorum quenching AHL lactonase impairs the adaptation of commensal bacterium to host innate immunity. https://doi.org/10.1101/2025.02.05.636741

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