Herbicides Used with GM Crops Alter Antibiotic Resistance of Disease-Causing Bacteria

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Diverse E.coli

Diverse E.coli

Authors answer ques­tions on new study, which shows that expo­sure to Roundup and oth­er her­bi­cides could con­tribute to antibi­ot­ic resis­tant disease.

A new study has found that expo­sure to the her­bi­cides used on GM crops changes how sus­cep­ti­ble dis­ease-caus­ing bac­te­ria are to antibi­otics. In many cas­es the bac­te­ria became more antibi­ot­ic-resis­tant, though in oth­er cas­es they became less so. The study was car­ried out by Prof Jack Heine­mann, Dr Brigit­ta Kuren­bach, and oth­er sci­en­tists from New Zealand and Mex­i­co. Below Prof Heine­mann and Dr Kuren­bach respond to ques­tions from GMWatch.

GMW: What did you find?

Heine­mann: When we exposed either of two dif­fer­ent species of bac­te­ria to com­mon her­bi­cides that we pur­chased at a local store, we found that the bac­te­ria changed their response to antibi­otics. They often became antibi­ot­ic resis­tant, but we also occa­sion­al­ly saw increased sus­cep­ti­bil­i­ty or no effect.

GMW: Which her­bi­cides and antibi­otics are you talk­ing about?

Kuren­bach: We test­ed com­mer­cial for­mu­la­tions of her­bi­cides based on the active ingre­di­ents dicam­ba, 2,4‑D and glyphosate. The antibi­otics were rep­re­sen­ta­tive of five major groups: β‑lactams (ampi­cillin), chlo­ram­pheni­col, tetra­cy­cline, fluro­quinolones (ciprofloxacin) and amino­gly­co­sides (kanamycin).

GMW: Why does your study matter?

Heine­mann: Every day you see in the news that there are con­cerns about the ever increas­ing fre­quen­cy of antibi­ot­ic resis­tance in bac­te­ria that can cause dis­ease in peo­ple and our ani­mals. Any­thing that con­tributes to this prob­lem should be con­sid­ered because new antibi­otics are rare.

Kuren­bach: The effects found may be rel­e­vant if peo­ple or ani­mals are exposed to her­bi­cides at the high­er ranges of con­cen­tra­tion, those that occur when it is applied rather than what is nor­mal­ly found on food. Those kinds of expo­sures may be expe­ri­enced by, for exam­ple, farm ani­mals and pol­li­na­tors in rur­al areas and poten­tial­ly chil­dren and pets in urban areas.

Heine­mann: And we can’t pre­dict either the direc­tion or size of the observed effects based on bac­te­r­i­al species, antibi­ot­ic or her­bi­cide used. Thus, dif­fer­ent poten­tial dis­ease-caus­ing bac­te­ria may react dif­fer­ent­ly to the same her­bi­cide or to the same antibiotic.

GMW: Is this the first study to show this?

Kuren­bach: We’ve looked hard to find oth­er stud­ies like this, but haven’t found any. Oth­er stud­ies have report­ed on oth­er sub­stances that also change bac­te­ri­a’s tol­er­ance to antibi­otics (e.g. aspirin), but her­bi­cides weren’t used.

GMW: What are the lim­i­ta­tions of your study?

Heine­mann: While we test­ed exam­ples from most major groups of antibi­otics, there are more indi­vid­ual antibi­otics than we could test. And our tests are in the lab­o­ra­to­ry. We hope to get fund­ing to test envi­ron­men­tal sam­ples or bac­te­ria from animals.

Kuren­bach: We only test­ed two species of bac­te­ria. They were lab­o­ra­to­ry strains of dis­ease-caus­ing species. We’d like to test the response of more species of bacteria.

We pro­vide genet­ic and bio­chem­i­cal evi­dence of how the bac­te­ria become resis­tant or sen­si­tive. But there may be more ways than we have so far described.

GMW: Have these results been replicated?

Heine­mann: As part of this study we engaged anoth­er sci­en­tist at anoth­er uni­ver­si­ty in a blind­ed repli­ca­tion. We sent her the bac­te­ria and chem­i­cals through an inter­me­di­ary who kept their iden­ti­ties a secret. Using our pro­to­cols, she was able to con­firm our find­ings. She also lat­er joined the author team.

The study

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
Brigit­ta Kuren­bach, Del­phine Mar­joshi, Car­los F. Amá­bile-Cuevas, Gayle C. Fer­gu­son, William God­soe, Pad­dy Gib­son, Jack A. Heinemann
mBio 6(2):e00009-15. doi:10.1128/mBio.00009–15.

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-galactosidase assays with soxS­lacZ fusion strains of E. coli. Dicam­ba was a mod­er­ate induc­er of the sox reg­u­lon. Growth assays with Phe-Arg -naphty­lamide (PAN), 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.

IMPORTANCE Increas­ing­ly com­mon chem­i­cals used in agri­cul­ture, domes­tic gar­dens, and pub­lic places can induce a mul­ti­ple antibi­ot­ic resis­tance phe­no­type in poten­tial pathogens. The effect occurs upon simul­ta­ne­ous expo­sure to antibi­otics and is faster than the lethal effect of antibi­otics. The mag­ni­tude of the induced response may under­mine antibi­ot­ic ther­a­py and sub­stan­tial­ly increase the prob­a­bil­i­ty of spon­ta­neous muta­tion to high­er lev­els of resis­tance. The com­bi­na­tion of high use of both her­bi­cides and antibi­otics in prox­im­i­ty to farm ani­mals and impor­tant insects, such as hon­ey­bees, might also com­pro­mise their ther­a­peu­tic effects and dri­ve greater use of antibi­otics. To address the cri­sis of antibi­ot­ic resis­tance requires broad­en­ing our view of envi­ron­men­tal con­trib­u­tors to the evo­lu­tion of resistance.