The sting in the tail of antibiotic use
Recently, I found a paper published in mBIO that describes how antibiotic use in farming is involved in the spread of resistance genes. In this case the work focuses on the humble honeybee (Apis mellifera). Since the 1950s, beekeepers in the USA have been using the antibiotic oxytetracycline – a ‘broad-spectrum’ antibiotic that kills most species of bacteria – to prevent infections that can cause ‘foul brood’, a disease that kills bee larvae. As you can imagine, using a single antibiotic for more than 50 years has led to some selective pressure. In this work, researchers from Yale University were investigating the prevalence of disease resistance in bee gut bacteria.
This might seem like a strange place to look, but it actually has its advantages. Unlike the supremely complex ecosystem of the human gut microbiome, the bee’s is pretty simple, with eight species making up over 95% of the gut bacteria in adult worker bees. The small number of species and the knowledge of how hives have been treated allowed the researchers to monitor the impact of decades of antibiotic use.
The researchers tested honeybees from hives from across the USA and some from Switzerland, the Czech Republic and New Zealand. Unsurprisingly, bees from hives treated with oxytetracycline had high levels of resistance genes, whereas American bees that had not been treated for more than two years had lower levels. Bees from the countries outside the USA that have no antibiotic use had very low levels of resistance genes, as did a colony in Arizona that has had no oxytetracycline exposure for more than 25 years.
What is striking about the work is that it wasn’t just one tetracycline resistance gene that was detected – it was eight. Six of these genes encoded different efflux pumps (proteins that pump the antibiotic out of the bacteria before it can do any damage), and two alter the ribosome and prevent the drug from working by modifying its target. In a couple of instances a gene that confers resistance to beta-lactam antibiotics such as ampicillin was also detected, probably because it was attached to one of the other genes.
Bacteria are notoriously promiscuous and readily share genes with other species around them. The resistance genes detected in this study were consistently associated with other plasmids or transposons – pieces of DNA that help genes move between bacteria. Match this promiscuity with the fact that bees are moved all over the USA, either by suppliers or by commercial pollination services, and you might have found the reason these resistance genes are spread across the country. The researchers also identified that the resistance genes were almost identical to those previously found in human pathogens or bacteria found in farm animals.
Although this paper in no way suggests that the presence of these resistance genes is directly harming the bees, it does speculate that there is potential for the selective pressure brought about by long-term antibiotic use to harm the delicate balance of the insect’s gut microbiota. Given its simplicity, a small change could make a big difference. And we really need bees; the economic value of insect pollinators in 2005 was estimated to be €153 billion, and some plants can’t reproduce without them.
The work also highlights the problems that have arisen through antibiotic use in farming, where they have traditionally been used as growth promoters and in veterinary medicine. Before the ban on the use of antibiotics as growth promoters, it was estimated that between 50% and 70% of antibiotics were used in agriculture, which amounted to thousands of tonnes a year and eight times the amount used in human medicine. It is reassuring that clinicians are becoming more enlightened about antibiotic use, but now we really need to spread the message to everyone else.
Tian, B., Fadhil, N., Powell, J., Kwong, W., & Moran, N. (2012). Long-Term Exposure to Antibiotics Has Caused Accumulation of Resistance Determinants in the Gut Microbiota of Honeybees mBio, 3 (6) DOI: 10.1128/mBio.00377-12