Sublethal Exposure to Commercial Formulations of the Herbicides Dicamba, 2,4-Dichlorophenoxyacetic Acid, and Glyphosate Cause Changes in Antibiotic Susceptibility in Escherichia coli and Salmonella enterica serovar Typhimurium

Abstract

Biocides, such as herbicides, are routinely tested for toxicity but not for sublethal effects on microbes. Many biocides are known to induce an adaptive multiple-antibiotic resistance phenotype. This can be due to either an increase in the expression of efflux pumps, a reduced synthesis of outer membrane porins, or both. Exposures of Escherichia coli and Salmonella enterica serovar Typhimurium to commercial formulations of three herbicides—dicamba (Kamba), 2,4-dichlorophenoxyacetic acid (2,4-D), and glyphosate (Roundup)—were found to induce a changed response to antibiotics. Killing curves in the presence and absence of sublethal herbicide concentrations showed that the directions and the magnitudes of responses varied by herbicide, antibiotic, and species. When induced, MICs of antibiotics of five different classes changed up to 6-fold. In some cases the MIC increased, and in others it decreased. Herbicide concentrations needed to invoke the maximal response were above current food maximum residue levels but within application levels for all herbicides. Compounds that could cause induction had additive effects in combination. The role of soxS, an inducer of the AcrAB efflux pump, was tested in β-galactosidase assays with soxS-lacZ fusion strains of E. coli. Dicamba was a moderate inducer of the sox regulon. Growth assays with Phe-Arg β-naphtylamide (PAβN), an efflux pump inhibitor, confirmed a significant role of efflux in the increased tolerance of E. coli to chloramphenicol in the presence of dicamba and to kanamycin in the presence of glyphosate. Pathways of exposure with relevance to the health of humans, domestic animals, and critical insects are discussed.

Identification of the first glyphosate transporter by genomic adaptation

“…In contrast, a role of glyphosate in affecting the soil microbial activity is controversially discussed because studies are available suggesting a positive and a negative effect of the herbicide on the microbial activity of the soil (Haney et al, 2002;Barriuso et al, 2011;Schlatter et al, 2017;Dennis et al, 2018). Furthermore, sublethal concentrations of glyphosate were shown to reduce susceptibility of enterobacteria to antibiotics (Kurenbach et al, 2015). Experimental evidence also suggests that aminomethyl-phosphonic acid (AMPA), a breakdown product of glyphosate, may induce chromosomal damage in fish (Guilherme et al, 2014).…”

Effects of Glyphosate or “Organic Herbicide” on Rumen Bacterial Isolates In Vitro

“…Some studies of glyphosate and bacteria growth have drawn conclusions about the toxicity of glyphosate towards microbes without suitable controls or specifically testing individual components such as glyphosate from a mixture as having an influence without examining it alone or in comparison with positive and nega- tive control. Kurenbach et al 15 have reported that glyphosate can reduce antibiotic susceptibility in Escherichia coli and Salmonella enterica serovar Typhimurium. While these researchers did not investigate glyphosate alone (they evaluated a commercial glyphosate containing product), the claim glyphosate reduced antibiotic sensitivity is not clearly supported by their data; furthermore, many of the test combinations they evaluated appeared to increase antibiotic sensitivity.…”

Ecosocial food policy: improving human, animal, and planetary well-being

“…Evidence concerning the neurotoxicity for humans of even low-level exposure to pesticides shows problems with psychomotor speed and visuospatial ability as well as working and visual memory (Bouchard et al 2010;Ross et al 2013). Increasingly common chemicals used in agriculture can induce a multiple antibiotic-resistance phenotype in potential pathogens (Kurenbach et al 2015).…”