Structural effects of sulfonamides on the proliferation dynamics of sulfonamide resistance genes in the sequencing batch reactors and the mechanism

Antibiotic resistance genes (ARGs) can be easily promoted by antibiotics, however, the structural effects of antibiotics on the proliferation of ARGs dynamic and the associated mechanisms remain obscure in, especially, activated sludge sequencing batch reactors. In the present study, the effects of 9 sulfonamides (SAs) with different structures on the proliferation dynamic of sulfonamide resistance genes ( Sul s) in the activated sludge sequencing batch reactors and the corresponding mechanisms were determined (30 days), and the results showed that the largest proliferation value (∆ A R ) of Sul s dynamic for SAs (sulfachloropyridazine) was approximately 2.9 times than that of the smallest one (sulfadiazine). The proliferation of Suls was significantly related to the structural features ( minHBint6, SssNH, SHBd and SpMax2_Bhm ) that represent the biological activity of SAs. To interpret the phenomenon, a mechanistic model was developed and the results indicated that the biodegradation of SAs ( T 1/2 ) rather than conjugative transfer frequency or mutation frequency tends to be the key process for affecting Sul s proliferation. T 1/2 was proved to be dependent on the interactions between SAs and receptors ( E binding ), the cleavage mode (bond dissociation energy), and the site of nucleophilic assault. Besides, the metagenomic analysis showed that SAs posed significant effect on antibiotic resistome and Tnp31 played a vital role in the proliferation of Suls . Overall, our findings provide important insight into a theoretical basis for understanding the structural effects of SAs on the proliferation of ARGs in SBR systems.