The rapid removal mechanism of tylosin and the dynamics of antibiotic resistance genes during the aerobic thermophilic fermentation of tylosin mycelial dregs by integrated meta-omics study

Tylosin mycelia dregs (TMDs) are a potential hazard for tylosin and antibiotic resistance genes (ARGs) proliferation in the environment. For efficient treatment of TMDs, the mechanism of rapid removal of tylosin and the dynamics of ARGs during the fermentation of TMDs were investigated using integrated meta-omics technology. The results showed that the residual tylosin decreased rapidly regardless of the type of bulking agents, and the minimum detection limit was observed at day 14. The tylosin might be rapidly removal through the de-mycarose of Saccharomonospora (GH3), the esterase hydrolysis of Saccharomonospora (C7MYQ7), and the oxidation of catalase-peroxidase from Bacillus (A0A077JB13). The correlation between these bacteria and tylosin was further verified in network analysis. In addition, ARGs decreased in thermophilic stages and rebounded in mature stages. The correlation analysis showed that moisture content and mobile genetic elements (MGEs) were vital to control the rebound of ARGs. And the removal efficiency of resistant bacteria (Streptomyces, Pseudomonas, norank_f__Sphingobacteriaceae, Paenalcaligenes) and Intl1 (98.8%) in TC21 with corncob as bulking agent were significantly higher than that in the other three treatments (88.3%), which effectively inhibited the diffusion of ARGs. Therefore, appropriate bulking agents indeed decreased the abundance of resistant bacteria by changing the composition of microbial communities, which was of great significance to effectively reduce the resistance in TMDs.