How do superbugs learn to be ‘antibiotic bulletproof’?
Our researchers have recently been working with scientists from the USA to study superbug transmission. Actually, they studied the emergence of lots of different superbugs within one hospital over five years.
What was strange was that they found many different types of bacteria all sharing similar genetic ‘armor’. If antibiotics are like bullets, this was armor that could prevent even our strongest, last-line effective antibiotics (Carbapenems) from getting through. These bacteria, known as CPE (carbapenemase-producing Enterobacteriaceae) all knew how to produce their own, specific ‘bacterial armor’, which was rendering our last-line antibiotics ineffective. This meant that patients had to be treated with older, more toxic, or less effective antibiotics, and didn’t do as well. We needed to understand how this was happening.
We knew from lots of other studies that it can take a long time (in terms of bacterial lifetimes) for bacteria to develop entirely new armor – so surely they didn’t all learn to create this independently?
Our researchers studied the DNA of 281 different bacteria. Like humans, bacteria contain DNA – a complete instruction manual on ‘how to be a bacteria’. Unlike humans, they can also carry extra small loops of genetic information we call plasmids – DNA ‘booklets’ containing handy (but not essential) information, like how to scavenge extra nutrients, or inactivate antibiotics. Previous work has shown that bacteria can share these booklets between one another to transfer useful information.
What our researchers found was that the ‘bacterial armor’ recipe for bulletproof material (contained on a gene called “KPC”) was being shared via these plasmid ‘booklets’. They also found that the bacteria were also effectively ripping out the page with the armor recipe and putting it in new plasmid ‘booklets’, and sharing these as well. The researchers compared this to ‘russian dolls’ – recipe within page within booklet within bacteria…all being shared around. What was also remarkable was that completely different species of bacteria within the same family could all share the KPC ‘bulletproof recipe’ between each other on plasmid booklets. The rate at which these bacteria shared information around in this way was far higher than had been expected, or seen, before.
The family of bacteria (Enterobacteriaceae) sharing this information then caused difficult-to-treat, antibiotic-resistant blood, urine and chest infections. In fact, this family of bacteria is the leading cause of bloodstream infections in the world. They also live harmlessly around us, and play important roles in the ecosystem, in the guts, and human health. Many scientists believe they pose the greatest threat to human health in the near future, because they can spread easily, infect almost anyone, and they are becoming untreatable much faster than other bacteria.
This study helps us understand how genetically well-equipped bacteria are developing and spreading new armor faster than we can come up with new antibiotic ‘weapons’. Bacteria can effectively talk to one another, sharing information, adapting it, and sharing it again. It tells us we need to find out where these bacteria are sharing information and spreading, and prevent this. We need rigorous hygiene and monitoring, not just of patients, but the environment around them as well.
We know doctors, patients and the farm industry all overuse antibiotics. This research tells us in the strongest, simplest terms we need to learn to use less – otherwise very soon there will be no effective antibiotics left. If you don’t fire antibiotic bullets, bacteria don’t need to learn to make bulletproof armor.
Update 10/4/16 : The full paper is at: http://aac.asm.org/lens/aac/60/6/3767#figures
The preprint (released at the time of this article) http://biorxiv.org/
A previous published study of this outbreak is also available: http://www.ncbi.
Read about another University of Oxford study on plasmids and antibiotic resistance: http://www.ox.ac.uk/news/science-blog/puzzle-plasmids
This publication presents independent research commissioned by the Health Innovation Challenge Fund, a parallel funding partnership between the Department of Health and Wellcome Trust, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre based at Oxford University Hospitals NHS Trust and University of Oxford, and NIHR Oxford Health Protection Research Unit on Healthcare Associated Infection and Antimicrobial Resistance.
Anna Sheppard, Bioinformatician, who does the complex DNA analysis and has written the publication.
Nicole Stoesser, Doctor and Scientist from the John Radcliffe Hospital, Oxford, who extracted the DNA from many of the samples and analysed the data
Amy Mathers, Doctor and Scientist from Virginia, USA, who collected the samples and leads the Infection Prevention and Control Team
All images: www.pixabay.com, no attribution and free for commercial/noncommercial use