Expanding knowledge about new types of antibiotic resistance genes is of great significance in dealing with the global antibiotic resistance crisis. Herein, a novel oxidoreductase capO was discovered to be responsible for oxidative inactivation of chloramphenicol and thiamphenicol. The antibiotic resistance mechanism was comprehensively deciphered using multi-omics and multiscale computational approaches. A 66,383 bp DNA fragment carrying capO was shared among four chloramphenicol-resistant strains, and the co-occurrence of capO with a mobile genetic element cluster revealed its potential mobility among different taxa. Metagenomic analysis of 772 datasets indicated that chloramphenicol was the crucial driving factor for the development and accumulation of capO in activated sludge bioreactors treating antibiotic production wastewater. Therefore, we should pay sufficient attention to its possible prevalence and transfer to pathogens, especially in some hotspot environments contaminated with high concentrations of chloramphenicols. This finding significantly expands our knowledge boundary about chloramphenicols resistance mechanisms.

扩大对新型抗生素耐药基因的认识对于应对全球抗生素耐药性危机具有重要意义。在此，发现一种新的氧化还原酶capO负责氯霉素和甲砜霉素的氧化失活。使用多组学和多尺度计算方法全面破译了抗生素耐药机制。携带capO的 66,383 bp DNA 片段在四个耐氯霉素菌株之间共享，并且capO与移动遗传元素簇的共现揭示了其在不同分类群之间的潜在流动性。对 772 个数据集的宏基因组分析表明，氯霉素是氯霉素发展和积累的关键驱动因素。处理抗生素生产废水的活性污泥生物反应器中的capO 。因此，我们应该对其可能的流行和向病原体的转移给予足够的重视，尤其是在一些被高浓度氯霉素污染的热点环境中。这一发现显着扩展了我们关于氯霉素耐药机制的知识边界。