Glyphosate drives antimicrobial resistance

In this article, we question the role of glyphosate in the emergence of antimicrobial resistance in soil bacteria.

Considering that glyphosate was officially registered by Monsanto itself some years ago as an antibiotic, it appears to us that the multi-million tons of glyphosate applied yearly in agriculture, nearly a billion tons annually, would participate of rising Antimicrobial Resistance (AMR), and this could be seen notably in low middle income countries (LMIC) where there be low, sub-optimal use of antibiotics (ABs).

Recently, an article published in the Journal of Antimicrobial Chemotherapy caughted our attention. The article's abstract states: " We provide evidence that glyphosate (a herbicide but also an antibiotic drug) could be a possible driver of antibiotic resistance in countries where this herbicide is widely used because of modification of the microbial environment. Emergence of resistance in bacteria and fungi is correlated with glyphosate use in the world over the last 40 years."

Title: Role of glyphosate in the emergence of antimicrobial resistance in bacteria? Authors: Jean-Marc Rolain, et al. 2021 (Institut Hospitalo-universitaire Méditerranée Infection, Marseille, France ; Aix Marseille Université', Institut de Recherche pour le Développement (IRD), Assistance Publique-Hôpitaux de Marseille (APHM), Microbes Évolution Phylogénie et Infections (MEPHI), Marseille, France)

Excerpts from the Marseille study below:

"For several years, we have witnessed the emergence of multipharmacoresistant bacteria (MDR) from the intertropical zone, while the use of antibiotics in humans remains quite low in this part of the world. This discrepancy between the use of antibiotics in humans and the frequency of antibiotic resistance is the subject of debate and several hypotheses are currently discussed in the scientific community. In India, China, and Africa, resistance has increased dramatically while clinical use of some antibiotics has remained relatively low (1). The first hypothesis to explain this discrepancy pointed out that if antibiotic use remained modest, they were poorly managed.

The second hypothesis was the enormous use of drugs in the agricultural industry (2); this explanation can probably be accepted for resistance to colistin (3) and tetracyclines, but probably not for carbapenem antibiotics, which do not appear to have disproportionate veterinary use (4). Conversely, New Delhi metallo-Ɓ-lactam (NDM)-mediated resistance to imipenem has emerged in India (5), while recent work in Africa has shown that live wild animals in the city of Nairobi carry Escherichia coli MR, which cannot be explained by artificially increased consumption for agricultural reasons (6).

(...) All these data show that there is a discrepancy in the intertropical zone between a low level of antibiotic use in humans and a high level of antibiotic resistance in bacteria isolated in different ecosystems.

(...) there are clearly other sources that may exert selective pressure in the environment to explain the contemporary emergence of antimicrobial resistance in bacteria (4). In this regard, several new hypotheses have been proposed. The first is that there are bacteria in the intertropical zone that naturally secrete broad-spectrum b-lactam antibiotics, such as carbapenems, because we know several bacteria that secrete this type of antibiotics, including: Streptomyces, Serratia or Erwinia (10), and selection may come from an ecosystem not related to the use of antibiotics by humans.

The second hypothesis concerns the role of glyphosate as a possible driver of antibiotic resistance in microorganisms, as this compound has been widely used by humans in agriculture over the past 40 years (11). Glyphosate is a phosphonic acid that is widely used as a herbicide worldwide (and is also an antibiotic drug) and is used in particular countries in the intertropical zone at doses that exceed any that might be used in normal agriculture, but also in the cultivation of Genetically Modified Organisms (GMOs) 11. The mode of action of glyphosate is the inhibition of the shikimate pathway, in particular the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS); this enzyme is commonly present in some bacteria and fungi, but is absent in mammals 12. In fact, GMOs have been modified to carry this bacterial EPSPS gene for glyphosate resistance and thus glyphosate plays a role in selecting plants with this resistance by allowing only GMOs to grow. Under these conditions, one can imagine quantities of glyphosate being poured into rice fields, for example, or into corn crops, which are probably the most widespread GMOs in the world, grown massively in the intertropical zone, especially in Asia. In fact, glyphosate has a direct antibiotic effect on bacterial EPSPS like fosfomycin (another phosphonic acid used in humans as an antibiotic), which is well known since a patent has been taken out by Monsanto on the antimicrobial activity of glyphosate against a wide range of bacteria, fungi and parasites that contain the EPSPS enzyme (13).

(...) It has recently been shown that there is a correlation between the emergence of resistance in bacteria and fungi and the use of glyphosate worldwide over the last 40 years (11). This is correlated with a huge amount of glyphosate residues in the environment (soil, water), but also in plants (11). There is also an inductive or repressive effect on antibiotic resistance, which has been demonstrated in E. coli and Salmonella enterica (14).

THEBRIEF Editor noted:

Considering that glyphosate was officially registered by Monsanto itself some years ago as an antibiotic, it appears to us that the multi-million tons of glyphosate applied yearly in agriculture, nearly a billion tons annually, would participate of rising AMR, and this could be seen notably in LMIC where there be low, sub-optimal use of antibiotics (ABs).

In a recent (French language webinar, June 18th) on AMR & the Environment, to honor the memory of the Lebanese-French Dr Jacques Acar, 1931-2020, who died of COVID-19 last year, contracted at a scientific meeting in the US, we had the pleasure of a participant to the Mexican Scientific Council saying a few words on the Mexican gov't fight with industry to ban glyphosate for a whole variety of reasons but reasons that did not include AMR.

The compartimentalisation of knowledge today is such that people involved in agriculture lack knowledge on antibiotic resistance and people working in AMR do not generally follow debates on GMOs or agriculture.

In our highliting the issue and the importance of the Marseille study (excerpts below) it is ironical that Dr Acar, a true world expert, was central to the development of new ABs from industry, travelled as an expert, or worked with the OIE and meat industries. Acar would tell me: "There is too much focus on individual use of antibiotic, by the patient, the prescriber, or the cattleman for that matter, ignoring the fact that pesticides, chemical residues and so forth, are drivers of antibiotic resistance of soil, water bacterias!"

Référence: peer-reviewed article in Journal of Antimicrobial Chemotherapy

WEBINAIRE REPLAY - Séminaire à la Mémoire de Jacque Acar - pour les Francophones

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