Insights into Antibiotic Resistance Through Metagenomic Approaches

Robert Schmieder; Robert Edwards


Future Microbiol. 2012;7(1):73-89. 

In This Article

Animal- & Agriculture-related Resistance

Only approximately half of antibiotics produced each year are used for human health. The other half is used for industrial farm animal production. Some are used for therapeutics, but mostly the antibiotics are added at subtherapeutic levels to feedstuffs where they act as growth promoters.[77] The use of subtherapeutic doses of antibiotics is extremely controversial – it helps to keep the costs of meat and poultry in the USA low, perhaps reduces the overall number of animals that need to be reared, reduces fat in the meat, and reduces environmental impacts, but at the cost of providing an enormous source for the evolution of antibiotic resistance elements that may affect human health.

Antibiotics were first approved for the use as growth promoters in food animal production in the early 1950s, and since then the extensive use of subtherapeutic levels of antibiotics has been shown to promote antibiotic-resistance[78,79] and animal feed has been found to contain antibiotic resistance genes.[80] In 1986, Sweden was the first country to ban the use of antibiotic growth promoters in food animal production, and 20 years later the EU banned the feeding of antibiotics to livestock for growth promotion (although they are still used therapeutically). In the USA, cattle are usually treated with monensin, which is not directly related to antibiotics used in human therapeutics, while poultry are often fed bacitracin and tetracycline, which are both used in human medicine.

Because the issues surrounding the agricultural use of antibiotics are complex, and the spread of resistance mechanisms might potentially affect human health, metagenomics has been used to try to understand the flow of resistance genes associated with this source of antibiotics. One of the problems with agricultural antibiotic use is that the antibiotic is not restricted solely to the animal or farm where it is applied: residues from farms can contain antibiotic-resistance genes that may contaminate natural environments, wastewater treatment plants, and as we have seen, impact environmental microbiota.[81] The fecal component of cattle manure carries a large community of bacteria and is thus a natural vehicle for transmission of bacteria into the environment and onto other animals.[82] In particular, a variety of insects feed on cow manure, and insect guts are environmental reservoirs of antibiotic resistant bacteria with the potential for dissemination of resistance genes.[29] Manure applied to agricultural fields can also contaminate the surface of food crops, including vegetables and fruits[83] and has led to many of the well publicized outbreaks of food-borne illness in the USA and elsewhere. In addition, antibiotic-resistance genes can be aerosolized and carried away from the farm; they have been found downwind (but not upwind) of a large agricultural facility.[84] A sequence-based metagenomic study of the chicken cecum microbiome showed that resistance to tetracyclines and fluoroquinolones were dominating that environment, both classes of antibiotics that are routinely used in poultry production.[85] A further comparison of the virulence-associated sequences showed that the chicken cecum was more similar to the microbiome of bovine rumen than to that of mouse cecum or human fecal samples,[85] perhaps not surprising given the physiological differences in the intestine, rumen and cecum. Other studies suggest that the use of antibiotics in agriculture may have resulted in the spread of strains, such as vancomycin-resistant enterococci in both farm animals exposed to antibiotics and humans in contact with the animals,[78,86] as well as the maintenance of antibiotic-resistance genes in apparently antibiotic-free animals.[87]

Detailed discussion of the problems and challenges associated with agricultural antibiotic use can be found at the Pew Charitable Trusts website,[103] and at the Animal Health Institute's website.[104]