Effects of herbicides on both adaptive and acquired antibiotic resistance

Abstract

Antibiotic resistance is an increasingly serious global health issue that will not be solved without serious and considered intervention. In order to effectively combat increasingly resistant bacteria, a better understanding of the factors influencing the development of antibiotic resistance is necessary. Previous work from this lab has shown that commercial herbicide formulations can induce adaptive antibiotic resistance in Escherichia coli and Salmonella enterica serovar Typhimurium (Kurenbach et al., 2015).

To investigate the breadth of this response, Staphylococcus aureus was exposed to the same set of commercial herbicide formulations and antibiotics and three additional antibiotics commonly used to treat S. aureus infections. The pattern of herbicide-induced changes in antibiotic tolerance was similar but not identical to those observed for E. coli and S. enterica. The magnitude of changes in minimum inhibitory concentration (MIC) was often smaller for antibiotics that were used in both sets of experiments, while the largest changes were observed for the new antibiotics. These effects were observed at herbicide concentrations below application rates and, in some cases, at concentrations within the maximum residue limits (MRLs) allowable in animal feed and human food as defined by the Codex Alimentarius Commission (Codex Alimentarius Commision, 2016).

Whether the adaptive responses to the herbicides can lead to shifts in the population frequency of acquired antibiotic resistance was also tested. Specific combinations of herbicide and antibiotic that caused either increases or decreases in antibiotic tolerance were investigated in more detail. In two combinations of herbicide and antibiotic, ciprofloxacin + Kamba and ciprofloxacin + Roundup, that caused adaptive resistance to the antibiotic an increased frequency of acquired resistance was observed in S. enterica. When two strains of E. coli with differing antibiotic resistance were exposed to a combination of herbicide and antibiotic, tetracycline + Roundup or streptomycin + Kamba, that caused a decrease in antibiotic tolerance, increased selection in favour of the resistant bacteria was observed.