The £4 million project is funded by the Medical Research Council and led by Dr Robert Fagan with a team of molecular and clinical microbiologists across the Universities of Sheffield, Warwick, Manchester and Leeds. They will investigate the growing threat to vancomycin which is the main antibiotic used to treat C. difficile Infection (CDI). The disease currently results in over 2,000 deaths per year in the UK and places a significant burden on the NHS.
While vancomycin is the gold standard treatment, very little is known about the capacity of C. diff to develop resistance. Currently, NHS laboratories do not routinely test for this, despite scattered reports from other countries suggesting the drug is becoming less effective globally.
This latest research follows laboratory experiments showing that C. diff can rapidly evolve to tolerate 32 times the initial effective concentration of vancomycin within just two months.
To assess the risk to public health, the team will carry out parallel projects. The first will examine how the bacteria develops resistance under clinically-relevant conditions, such as while living alongside the complex community of microbes in the human colon.
This will be combined with an investigation into ‘fitness trade-offs’ to determine if the effort of surviving the antibiotic makes the bacteria ‘less fit’ and therefore less able to grow or spread between people. By exploring these molecular mechanisms, the team aims to pinpoint exactly how individual genetic mutations allow the bacteria to survive while under attack.
Finally, these laboratory insights will be applied to the largest analysis of its kind, involving the direct measurement of resistance among 6,000 UK C. diff strains. By assessing this alongside the genome sequences of up to 10,000 new UK isolates and tens of thousands of existing global genomes, researchers will use the identified genetic signatures to track and predict the emergence of resistance in real time across the NHS.
The findings from the project are intended to inform future infection control policy and allow the NHS to predict and track antibiotic resistance through new genomic surveillance.