Herbicide Mediated Selection of Sulfonamide Resistant E. coli
Abstract
Asulam is an herbicide that is structurally analogous to sulfonamide antibiotics (sulfas), with the potential to contribute to the global antibiotic resistance crisis by cross-selecting for sulfa-resistant bacteria. To determine if asulam can select for antibiotic resistant bacteria, isothermal titration calorimetry (ITC) was used to assess the binding affinity of asulam with the target protein of sulfas, dihydropteroate synthase (DHPS). ITC confirmed asulam interacts with DHPS, and in vitro directed evolution experiments showed that prolonged asulam exposure can select for sulfa-insensitive DHPS in E. coli. Since mobile sul genes also encode for sulfa-insensitive DHPS, the potential effect of asulam on the dissemination of the sul genes in a simulated bacterial community was assessed. These data suggested that asulam can promote sulfa-resistance by increasing the frequency of chromosomal folP mutations, and/or acquisition of sul genes in E. coli, and uniquely induce deletions of multiple genes at concentrations exceeding environmental relevance.