A SAR-based mechanistic study on the combined toxicities of sulfonamides and quorum sensing inhibitors on Escherichia coli

Abstract

Quorum sensing inhibitors (QSIs) are promising alternatives to antibiotics, but they are discharged into the environment after their use cycle. This poses joint effects on the organisms in the environment. Therefore, it is of great importance to study the combined toxicities of QSIs and antibiotics. In this study, we investigated the single and combined toxicities of four potential QSIs and 11 sulfonamides (SAs) on Escherichia coli. The results revealed that the single toxicities of SAs were greater than those of QSIs, and the toxicities were found positively related to the binding energies (E) with their target proteins, for both antibiotics and QSIs. The combined toxicities of the binary mixtures were observed to be either antagonism or addition. The antagonism could be explained by the phenomenon that QSIs changed SAs molecules into ionic forms, preventing the SA molecules entering the bacteria. Furthermore, it was found that the ratios of the effective concentration (the actual concentration involved in the interaction with the proteins) in the antagonistic cases were higher than those in the additive cases. This study would benefit both rational use of the drug combination and ecological risk assessment of antibiotics and QSIs in the real environment.

Veterinary antibiotics in swine and cattle wastewaters of China and the United States: Features and differences

“…These antibiotics included six SAs, five TCs, five FQs, one macrolide, one lincomycin, one chloramphenicol, and one anthelmintics. According to previous literatures (Brown, 1996;Martins et al, 2015;Moudgil et al, 2018), SAs, TCs, and FQs are antibacterial reagents widely used in veterinary practice because of their advantages, including low price and broad spectrum; thus, Chen, Wang, et al (2017).…”

The comparison of semiempirical and ab initio molecular modeling methods in activity and property evaluation of selected antimicrobial sulfonamides

“…In the literature, we can also find other studies with the use of structure-activity together with molecular docking with complexes and toxicity analysis of different antimicrobial sulfonamides (Agrawal et al 2001;Krátký et al 2012;Boufas et al 2014;Singh 2015;Chen et al 2017;Mondal et al 2017;Swain et al 2017;Mizdal et al 2018;Naaz et al 2018).…”