Quorum-sensing gene regulates hormetic effects induced by sulfonamides in Comamonadaceae

Hormesis is a toxicological phenomenon whereby exposure to low-dose stress results in stimulation of various biological endpoints. Among these, the induction of cell proliferation by antibiotics is critical, but the underlying molecular mechanisms remain poorly understood. Here, we showed that sulfonyl-containing chemicals (e.g., sulfonamides) can induce cell-proliferation hormesis of Comamonas testosteroni. Investigation of the hormesis mechanism revealed that low-dose sulfonamides bind to the LuxR-type quorum sensing protein LuxR solo, thereby triggering the transcription of 3-ketoacyl-CoA thiolase, a key enzyme of the fatty acid {beta}-oxidation. This provides additional ATP, NADPH, and acetyl-CoA for purine and pyrimidine biosynthesis, allowing cells to synthesize sufficient nucleotides to support rapid cell growth. Our work reports on a previously unknown mechanism for the hormetic effect and highlights its generality in the Comamonadaceae family.