Agrichemicals and antibiotics in combination increase antibiotic resistance evolution

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.

Complete Sequences of Multiple-Drug Resistant IncHI2 ST3 Plasmids in Escherichia coli of Porcine Origin in Australia

“…Any one of a number of selection pressures including heavy metals and biocides may be sufficient to then facilitate the persistence and spread of multiple drug resistance plasmids (Argudín et al, 2019). This is further compounded by reports that agrichemicals can alter selection for drug resistant bacteria (Kurenbach et al, 2015(Kurenbach et al, , 2018. The potential for complex resistance structures to persist under multiple different selective pressures and across diverse environments underpin the importance of adapting a One Health approach to antimicrobial resistance gene surveillance in humans, food and companion animals, agriculture, effluent (municipal, hospital, and agricultural), and the environments impacted by effluent from diverse sources (Djordjevic et al, 2013;Wyrsch et al, 2016;Huang et al, 2017;Mir et al, 2018).…”

Adaptation of bacteria to glyphosate: a microevolutionary perspective of the enzyme 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase

“…Other Proteobacteria clusters have species with differential sensitivity status after f ew amino acid changes in the active site ( figure 2). This microevolutionary analysis shows that some bacteria may become putatively resistant to glyphosate through small changes, analogous to the antibiotic resistance mechanism 7,13 . Thus, the wide use of glyphosate may have a very large impact on the species diversity and composition of microbial communities not only because of a potential purifying selection effect against sensitive bacteria but also because (i) some bacterial groups may adapt rapidly to become resistant to glyphosate and (ii) glyphosate-based herbicides may enhance multidrug resistance in bacteria 18 .…”

“…Due to its affordable price, effectiveness and broad-spectrum ability to kill weeds, glyphosate has become the most commonly used herbicide worldwide [4][5][6] . Although glyphosate antibiotic properties are known 7,8 , its possible effects on microbiomes [9][10][11] have largely been neglected until recently 10,12 . As microbes have driven eco-evolutionary processes since the origin of life, we note the importance of thoroughly understanding the possible undesirable effects of glyphosate on ecosystem structures, functions and services 13 .…”

Antimicrobiële resistentie en residuen van diergeneesmiddelen (antibiotica) in een circulaire veehouderij : Tegengaan van verspreiding via mest en milieu

“…Recent onderzoek heeft aangetoond dat bepaalde chemische bestrijdingsmiddelen in het milieu het proces van resistentievorming faciliteren/versnellen. Onderzoekers in Nieuw Zeeland hebben gerapporteerd dat bacteriën die zijn bloot gesteld aan (niet-antimicrobiële) chemische bestrijdingsmiddelen (zoals glyfosaat of isopropylamine zout -Roundup van Monsanto/Bayer) sneller antibioticaresistentie kunnen ontwikkelen (in sommige gevallen tot 100.000 keer) (Kurenbach et al, 2018). Er wordt ook gerapporteerd dat de combinatie van een hoog gehalte aan voedingstoffen, een hoge bacterie dichtheid, en de aanwezigheid van verschillende antibiotica en zware metalen de ideale omstandigheden creëert voor een overdracht van genen tussen bacteriën (Umweltbundesamt, 2018, zie ook Qiao et al, 2018.…”