Abstract
Antibiotic resistance in our pathogens is medicine’s climate change: caused by human activity, and resulting in more extreme outcomes. Resistance emerges in microbial populations when antibiotics act on phenotypic variance within the population. This can arise from either genotypic diversity (resulting from a mutation or horizontal gene transfer), or from differences in gene expression due to environmental variation, referred to as adaptive resistance. Adaptive changes can increase fitness allowing bacteria to survive at higher concentrations of antibiotics. They can also decrease fitness, potentially leading to selection for antibiotic resistance at lower concentrations. There are opportunities for other environmental stressors to promote antibiotic resistance in ways that are hard to predict using conventional assays. Exploiting our previous observation that commonly used herbicides can increase or decrease the minimum inhibitory concentration (MIC) of different antibiotics, we provide the first comprehensive test of the hypothesis that the rate of antibiotic resistance evolution under specified conditions can increase, regardless of whether a herbicide increases or decreases the antibiotic MIC. Short term evolution experiments were used for various herbicide and antibiotic combinations. We found conditions where acquired resistance arises more frequently regardless of whether the exogenous non-antibiotic agent increased or decreased antibiotic effectiveness. This is attributed to the effect of the herbicide on either MIC or the minimum selective concentration (MSC) of a paired antibiotic. The MSC is the lowest concentration of antibiotic at which the fitness of individuals varies because of the antibiotic, and is lower than MIC. Our results suggest that additional environmental factors influencing competition between bacteria could enhance the ability of antibiotics to select antibiotic resistance. Our work demonstrates that bacteria may acquire antibiotic resistance in the environment at rates substantially faster than predicted from laboratory conditions.
Highlights
As fundamental tools for infection control, antibiotics underpin diverse human systems ranging from hospital care to concentrated animal feeding operations through to crop and pollinator disease management
Neither reducing the use of antibiotics nor discovery of new ones may be sufficient strategies to avoid the post-antibiotic era. This is because bacteria may be exposed to other non-antibiotic chemicals that predispose them to evolve resistance to antibiotics more quickly
Simultaneous exposure to a variety of antibiotics and either various commercial herbicide formulations (Kurenbach et al, 2015) or to either active ingredients and some surfactants (Kurenbach et al, 2017), alters the survival of E. coli and S. typhimurium compared to exposure to only the antibiotics
Summary
As fundamental tools for infection control, antibiotics underpin diverse human systems ranging from hospital care to concentrated animal feeding operations through to crop and pollinator disease management. The loss of this tool due to antibiotic resistance will result in higher mortality and morbidity, and deny access to many routine medical procedures for risk of subsequently untreatable infections (Teillant et al, 2015; Thomas, Smith & Tilyard, 2014). It has been suggested that judicious and low use of antibiotics that keeps most antibiotic exposures to less than the minimum inhibitory concentration (MIC) should preserve antibiotic susceptibility in bacteria (Andersson & Hughes, 2014). Keeping the use of antibiotics to below MSC concentrations is more challenging still
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