MCR-1: The consequence of antibiotic misuse and evolving resistance

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According to a recent paper published the Lancet, a superbug gene that confers resistance to colistin, an antibiotic used to treat Gram-negative bacterial infections when all other drugs fail, has been discovered in China (Liu et al., 2016; TheStar, 2016). The gene in question, called MCR-1, was found in E.coli in samples from meat, hospital patients, and livestock in southeastern China. Given that China is among the countries with the highest colistin use in agriculture, resistance to the drug may have originated in that part of the world; however, new reports show that the gene is not restricted to China as the following countries have similarly discovered MCR-1 in bacterial DNA: Algeria, Canada, Denmark, England, France, Laos, Portugal, Thailand, The Netherlands, and Wales (TheStar, 2016). Some of the bacterial DNA analyzed and found positive for the MCR-1 gene was derived from specimens archived before 2015; therefore, dissemination of the gene has outpaced discovery, and the issue at hand may already be an international crisis.

The Ugly

Although MCR-1 has been shown to counter the effects of colistin, a more important finding was that the gene has been located on bacterial plasmids (Liu et al., 2016). Plasmids are portions of DNA separate from the chromosome that can be shared with other bacteria through a process called “conjugation” (Biotechnology Learning Hub, 2014). In other words, colistin immunity can be passed on from one bacterium to the next, and virulent strains of bacteria can acquire the immunity from more benign strains. In the worst case scenario, whereby MCR-1 combines with another plasmid-based gene, called NDM-1, superbugs impervious to medical intervention may arise (CTVNews, 2016). NDM-1 grants resistance to a broad range of antibiotics, and some strains of bacteria possessing the gene are only susceptible to few antibiotics such as colisitin (Kumarasamy et al., 2010).

The Bad

Given the present expanse of MCR-1 and the fact that it has been circulating well before 2015 (CTVNews, 2016), implementing efforts to control the spread of the gene may have limited usefulness. The Chinese government has expressed their desire to ban colistin from agriculture use following the discovery (TheStar, 2016); however, the damage has already been done. A more effective solution may be to ban all antibiotics with significant human application from animal agriculture including polymyxins (the family of antibiotics that include colisitin), in order to reduce mortality due to untreatable superbugs.

According to the Canadian Antimicrobial Resistance Surveillance System report of 2015, antimicrobial distribution for animal use was 1.4 times greater than for human use in 2013 (Government of Canada, 2015). The report also notes that, in 2013, 99.4% of antimicrobials used in animals in Canada were for the purpose of food-production, and 68% of said antimicrobials belonged to classes medically important to humans.

Despite the alarming nature of the situation, Canada has done little to address the issue. In 2014, the Canadian government working with the Canadian Animal Health Institute issued a notice to stakeholders to eliminate antibiotic use for growth promotion in food animals, remove growth promoting claims of antimicrobials, as well as improve the oversight of veterinarians for the use of antibiotics in agriculture (CBCNews, 2014; Health Canada, 2014). At first glance, the notice seems promising in that it should reduce antibiotic use in livestock production; however, these changes in policy will unlikely result in any practical benefit. Although antibiotic use for growth promotion will be eliminated, antibiotics will still be used liberally for “disease prevention”. Greater veterinary involvement as indicated by the stakeholder notice is also unlikely to reduce the use of antibiotics in animal agriculture, as the policy will only require farmers to procure a prescription for certain drugs. In addition, farmers outside of Quebec do not require a prescription to purchase a variety of antibiotics important to humans for livestock use, and farmers are able to import cheaper and/or unapproved drugs internationally without being regulated or monitored.

The Good

Despite its circulation since 2010, the MCR-1 gene has not been linked to any deaths in Ontario (TheStar, 2016); nevertheless, this point does not justify apathy on the political level. The emergence of MCR-1 is merely a symptom of the true issue at hand: evolving antimicrobial resistance among bacteria.

Other than banning the use of antibiotics important to humans for animal agriculture, the following non-exhaustive list of antibiotic alternatives can be used in conjunction with political action to reduce antibiotic usage, and subsequently, multidrug resistance: antibacterial vaccines, immunomodulatory agent, bacteriophages, lysins, antimicrobial peptides, probiotics, prebiotics, synbiotics, plant extracts, bacterial quorum sensing inhibitors, biofilm inhibitors, virulence inhibitors, and feed enzymes (Cheng et al., 2014). Moreover, it is important to recognize the role that the consumer plays in shaping the food market, a role that is easily dismissed in light of the assumed government responsibility.

The purpose of drug use in animal agriculture is ultimately to improve profit margins by reducing production costs, increasing production volume, and reducing the cost for the public to encourage sales; therefore, consumers would be wise to exercise control over their food choices to discourage the use of antibiotics in meat and to limit exposure to antibiotic-resistant strains of bacteria. Government policy reflects public mindset, so take control of your health, and be a leading example to inspire others to do the same.

 

 

References

Biotechnology Learning Hub. (2014). Bacterial DNA – The role of plasmids. Retrieved from http://biotechlearn.org.nz/themes/bacteria_in_biotech/bacterial_dna_the_role_of_plasmids

CBCNews. (2014). Health Canada’s quiet move to end use of antibiotics to fatten up animals: Still loopholes as Ottawa takes tiny step to curb antibiotic use in livestock. Retrieved from http://www.cbc.ca/news/health/health-canada-s-quiet-move-to-end-use-of-antibiotics-to-fatten-up-animals-1.2700972

Cheng, G., Hao, H., Xie, S., Wang, X., Dai, M., Huang, L., Yuan, Z. (2014). Antibiotic alternatives: the substitution of antibiotics in animal husbandry? Front Microbiol, 5, 217.

CTVNews. (2016). MCR-1 gene that makes bacteria resistant to powerful antibiotics found in Canada. Retrieved from http://www.ctvnews.ca/health/mcr-1-gene-that-makes-bacteria-resistant-to-powerful-antibiotics-found-in-canada-1.2725097

Government of Canada. (2015). Canadian Antimicrobial Resistance Surveillance System Report 2015. Retrieved from http://healthycanadians.gc.ca/publications/drugs-products-medicaments-produits/antibiotic-resistance-antibiotique/antimicrobial-surveillance-antimicrobioresistance-eng.php#a7-2

Health Canada. (2014). Notice to stakeholders: Collaborative efforts to promote the judicious use of medically-important antimicrobial drugs in food animal production. Retrieved from http://www.hc-sc.gc.ca/dhp-mps/vet/antimicrob/amr-notice-ram-avis-20140410-eng.php

Kumarasamy, K., Toleman, M., Walsh, T., Bagaria, J., Butt, F., Balakrishman, R., … Woodford, N. (2010). Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: A molecular, biological, and epidemiological study. Lancet Infect Dis, 10(9), 597-602.

Liu, Y., Wang, Y., Walsh, T., Yi, Li., Zhang, R., Spencer, J., … Shen, J. (2016). Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: A microbiological and molecular biological study. The Lancet, 16(2), 161-168.

Skeeze (Photographer). (2015). Bacteria [Photograph], Retrieved from https://pixabay.com/en/bacteria-electron-microscope-811861/

TheStar. (2016). ‘Disturbing’ drug-resistant superbug gene has been detected in Canada. Retrieved from http://www.thestar.com/news/world/2016/01/05/disturbing-drug-resistant-superbug-gene-has-been-detected-in-canada.html

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