The Evolution of Antibiotic Resistance
One of my favourite things about my job at the MRC is writing about all types of biomedical research, and not just cancer. This week I’ve been digging into the threat of antibiotic resistance, and it is truly sobering to read how bad a problem it is. Coincidentally I stumbled across this fantastic experiment carried out by a team of researchers at Harvard University. It illustrates how antibiotic resistance happens, and more importantly (and scarily!) how fast
it happens. I love this experiment for the simplicity behind it, and how illuminating the results are.
✤ To study the evolution of antibiotic resistance, the researchers set up a giant petri dish. This rectangular dish was filled with agar that was dyed black (so that the bacteria could be seen easily) and topped off with soft agar (so that the bacteria could move easily).
✤ The plate was divided up into nine sections for antibiotic concentration. The outmost edges of the plate had no antibiotic, and then the dose was gradually increased until the centre of the plate had 3000 units of antibiotic.
✤ The researchers then put E. coli
bacteria on the edge of the plate. These bacteria are able to move, and therefore when they used up all the nutrients in a local area, they spread through a mechanism called ‘chemotaxis’ – the bacteria are drawn towards the chemicals released by the nutrients in the nearby regions on the agar plate. But these nearby regions have antibiotics in them, so only bacteria that have evolved resistance can spread to these regions.
✤ It’s worth noting that the antibiotic starts out at a non-lethal dose, which means that a certain proportion of the bacteria will be able to survive it. Then, as the antibiotic gradually increases, it selects
the bacteria that have mutations in their genes that allow them to survive despite ever-increasing concentrations of antibiotic.
✤ The beauty of this experiment is that it is possible to see this happening in the relatively short space of 11 days
. What’s more, the researchers were able to sample the resistant bacteria and then sequence the genes to find out exactly how antibiotic resistance evolves.
✤ One of the most common mutations was in a gene known as dnaQ
which codes for a protein that helps copy DNA when the cells divide. This protein has proof-reading abilities, but when it is mutated, the proof-reading ‘relaxes’ - resulting in a typo-ridden genome that has immense potential for accumulating more and more mutations very rapidly. In addition to dnaQ
mutations, the bacteria also had mutations in genes involved in the folate biosynthesis pathway, which is the main target of the antibiotic used in this experiment.
✤ It’s also worth noting that mutations that increased antibiotic resistance came at a cost – these mutant bacterial strains were smaller due to reduced growth. But as soon as the mutants established themselves in the antibiotic-filled region, compensatory mutations kicked in and they were able to reach normal size.
✤ In the end, the bacteria at the centre of the plate were able to tolerate a dose of antibiotics that was 1000 times higher than that tolerated by the starting bacteria. It’s terrifying to realise how under the right conditions, bacteria can evolve so quickly. It’s also sobering to realise that antibiotics, a discovery that transformed modern medicine, may soon be obsolete thanks to the wide-spread misuse of antibiotics in agriculture and medical settings.
Full text research paper: http://science.sciencemag.org/content/353/6304/1147.full
More writing on antibiotic resistance: https://www.statnews.com/2016/09/12/superbug-antibiotic-resistance-history/