Genomic study tracks the rise of multidrug resistant E.coli

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• Date: 17 May,2021

Antibiotic resistance in E.coli has been steadily rising since the early 2000s despite attempts to control it, a new study suggests. In the biggest genomic survey of E.coli to date, that took more than 16 years in Norway, researchers have successfully tracked the spread of antibiotic resistant genes and have demonstrated that these genes are being transferred between E.coli strains.

The results, published today (10th May) in Lancet Microbe show that monitoring these resistant strains is important in the defense and control of drug resistant E.coli, which poses a significant issue in hospitals where it can cause severe infection and mortality. Additionally, understanding how these genes are transferred between breeds, and what has caused them to acquire drug resistance can help stop the growth of antibiotic resistance strains.

The bacterium, Escherichia coli is a common cause of blood infections globally, which seem to be increasing over the last decade. E.coli is commonly found in the gut, where it does not cause harm, but when it gets into the blood because of weakened immune system it can cause severe and life threatening ailments. As an extra challenge for health care providers, multi-drug resistance (MDR) has become a frequent feature of such infections, and in a worrying number of cases the available treatment options are getting limited.

In the biggest study of its kind, and only the second systematic longitudinal genomic study of bacteremia E.coli, researchers from the Wellcome Sanger Institute and the University of Oslo processed a nation-wide catalog of samples from more than 3,200 patients to track antibiotic resistance over 16 years. By harnessing the power of large scale DNA sequencing, they monitored the emergence of drug resistance and compared this to a similar study conducted in the UK.

The group found that MDR started to increase and show in more breeds in the early 2000s due to antibiotic pressure, and now multiple MDR E.coli strains are present in Norway. However, MDR E.coli seems to be more widely present in the united kingdom, despite similar policies in place around antibiotic use. The UK population however is considerably larger than Norway which could explain some of the differences. Further research is needed to allow for closer comparison and to identify the exact elements that cause rapid spread in certain locations compared to others.

MDR is comparatively rare in bacteria. But this new study has identified that lineages that previously were not thought to have MDR have acquired drug-resistance genes, demonstrating the increased ability of E.coli to share MDR genes that move horizontally between strains.

Professor Jukka Corander, co-author and Associate Faculty member in the Wellcome Sanger Institute, said:”The high number of samples from the Norwegian population and the amount of genomic detail about the strains of bacteria enabled us to make a whole lot more far-reaching conclusions than were ever possible before. This study demonstrates the power arising from a systematic national surveillance of resistant organisms, which both collects and makes the information available for in-depth analyses. Without these in place, it would have been impossible to approach the fundamental research questions formulated in the study and discover answers to them.”

The researchers hope to conduct similar research in the UK to build on previous studies and gain a complete data set of 16 years in the UK to be able to more closely monitor MDR resistant E.coli.

Being able to estimate the expansion timelines of the MDR clones of E. coli and to identify multiple occasions of novel acquisition of resistance genes is particularly exciting as this is the first time that this has been possible. Understanding and tracking the movement of these drug resistance genes and the strains that carry them are necessary for controlling the spread of drug-resistant bacteria, which is a huge issue in healthcare.”

Dr Rebecca Gladstone, Study lead author and Bioinformatician, University of Oslo, Norway

Professor Julian Parkhill, co-author and Professor at the Department of Veterinary Medicine at University of Cambridge, said:”Long-term studies such as this one provide in-depth understanding about the complex epidemiology underlying blood infections.