Research

Accessible version of AMR Timeline

2008: Discovery of NDM-1 and its structure

Researchers discover the first case of a bacterial infection with resistance caused by NDM-1, a powerful enzyme that degrades β-lactam antibiotics, one of the most frequently-prescribed classes and which includes penicillin. Professor Tim Walsh was part of the group that identified the enzyme, which is commonly produced by Escherichia coli and Klebsiella pneumonia, but can also spread between different bacterial strains. In 2011 scientists at the MRC Research Complex at Harwell determined the structure of NDM-1 using the STFC’s Diamond Light Source crystallography facility. Understanding its structure will help researchers develop drugs that could inactivate the enzyme or escape its action.

2009: Developing a vaccine against Salmonella

Professor Adam Cunningham at the University of Birmingham advances a novel approach for constructing a vaccine against Salmonella infections, based on world-leading immunology research. The vaccine development has been licensed to Novartis Vaccines Institute for Global Health.

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2010: How a virus fights E.coli

Researchers at the MRC Centre for Molecular Bacteriology and Infection (CMBI) reveal the structure of a protein called Gp2, produced by the ‘bacteriophage’ virus T7, which disables E.coli cells. In 2012 CMBI researchers demonstrate how Gp2 interacts with E.coli’s’s RNA polymerase (RNAP) to stop it from functioning and in 2017 discover that in addition to Gp2, T7 also uses protein Gp5.7 to disable any leftover RNAP.  Bacteriophage viruses infect and kill many bacterial species and mimicking the mechanisms that they use is thought to be a promising route to identifying new therapies.

2010: Identifying antimicrobial compound on ants

Bacteria carried on the surface of leafcutter ants produce antimicrobial compounds, according to a study by researchers at the University of East Anglia. The antimicrobials help the ants cultivate a fungus that provides them with food, protects their nest against infection and controls competing strains of fungi. In 2017 the researchers discovered a new family of antimicrobial agents in bacteria living on an African species of fungus-growing plant ant. These agents, called formicamycins, are active against some drug-resistant bacteria and, unlike other similar molecules, it appears more difficult for bacteria to develop resistance against them. This work involved MRC, BBSRC and NERC-funded researchers.

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2011: Developing a vaccine against bacterial meningitis

Dr Andrew Gorringe at the Health Protection Agency helps develop a novel vaccine against bacterial meningitis. The vaccine, MenBioVaxTM has the advantage that it is active against all subtypes of Neisseria meningitides, one of the most common causes of bacterial meningitis. It is currently being developed with funding from the Biomedical Catalyst by ImmBio, a vaccine development company based at the Babraham Research Campus in Cambridge.

2011: Developing a smartphone app to guide antibiotic prescribing

The Imperial Antibiotic Prescribing Policy (IAPP) smartphone app is developed by Imperial College Healthcare NHS Trust and the UKCRC Centre for Infection Prevention and Management. The app helps healthcare professionals choose the most appropriate course of treatment to ensure antimicrobials are prescribed appropriately. The app is used over 4,800 times in the first month. 85 per cent of users responding to a survey said the app added to their knowledge base regarding antimicrobial prescribing and 96 per cent found that it influenced their prescribing practice.

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2012: Showing how infection travels around the body in real-time

In an MRC-funded study, Professor Gad Frankel at Imperial College London uses a mouse infected with bacteria genetically modified to produce light to show how an infection moves around the body in real time. Regular scans of the mouse have shown how different vaccines and antibiotics change the way bacteria take over parts of the body.

2012: Developing an antimicrobial coating for prostheses

MRC-funded researcher Professor Robert Akid at the University of Manchester patents an antimicrobial coating for cementless prostheses, such as hip and knee replacements, to prevent infection. The controlled release ensures the antimicrobial is released only at the appropriate time (during and after surgery).

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2013: MRC researcher isolates 40 different bacteria-eating viruses

A team led by MRC-funded researcher Dr Martha Clokie at the University of Leicester isolates 40 different bacteriophages — viruses that specifically destroy bacteria — with the potential to work against hospital superbug C. difficile. Australian pharmaceutical company AmpliPhi Biosciences Corporation is funding the further development of “phage” therapy, and has recently conducted early clinical studies using a cocktail of phage strains to combat lung infections and life-threatening septicaemia.

2013: Using whole-genome sequencing to analyse how C.difficile spreads

A University of Oxford team, led by Dr David Eyre and Dr Sarah Walker, use whole genome sequencing to show that many cases of C. difficile infection are caused by bacteria transmitted from people who show no sign of infection, or from environmental sources such as water, animals, or food, rather than from symptomatic patients. Their study suggested that 45 per cent of cases had sufficient genetic diversity to represent transmission from sources other than symptomatic patients. This knowledge is important in developing strategies for preventing the spread of bacterial infections..

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2014: Studying the Salmonella cells that evade antibiotic action

Researchers at the MRC Centre for Molecular Bacteriology and Infection (CMBI) visualise ‘persister’ cells in Salmonella for the first time, using a fluorescent protein produced by the bacteria. Persister cells are a non-replicating form of the bacteria and ‘lie low’ to evade antibiotic action.

2015: Discovering how bacteria hold on to their hosts

MRC-funded researchers at the University of St Andrews and the John Innes Centre in Norwich discover how Streptococcus pyogenes, which cause many infections, use chemical harpoons to attach themselves to the body. This tactic is shared by many other bacteria that infect humans, such as Streptococcus pneumoniae, the most common cause of pneumonia in adults, and Clostridium difficile, notorious for causing severe gut infections in hospitalised patients. This discovery could pave the way for a new approach to treating bacterial infections by 'disarming' bacteria, leaving them unable to attach to their host, instead of trying to kill them with antibiotics.

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2015: Stopping bacteria from entering ‘stand-by’ and hiding from antibiotics

Researchers at the MRC Centre for Molecular Bacteriology and Infection (CMBI) discover that disabling yeaG, a gene in E.coli, blocks the bacteria from entering ‘stand-by’, the state in which they cannot be targeted by antibiotics. Bacteria enter stand-by when they encounter unfavourable conditions such as nutrient deprivation; it enables them to shut down their metabolism until conditions improve. However, antibiotics can only target bacteria when they are metabolically active. YeaG is also found in many other antibiotic-resistant bacteria, such as Salmonella. It is hoped that identifying yeaG’s genetic pathway will pave the way to new approaches to combat antibiotic-resistant bacteria.

2016: MRC research leads to China banning antibiotic from agriculture

Professor Tim Walsh at the University of Cardiff works with the Chinese Government to help implement a ban on using last-resort antibiotic colistin in animal feed. Professor Walsh and his team had previously identified in China a new gene called MCR-1 that gave bacteria resistance to colistin. China was one of the world’s biggest users of colistin in agriculture, primarily in animals feed as a growth-promoter. It is likely that colistin resistance evolved in this context. The ban has resulted in the withdrawal of more than 8,000 tonnes of colistin.

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2016: Creating a database of bacterial genome sequence data

Professor Sharon Peacock at the University of Cambridge publishes a database of whole genome sequencing data for Staphylococcus aureus bacterial samples, including of methicillin-resistant S. aureus (MRSA), isolated from various locations. The database is a valuable resource for the surveillance and outbreak investigation of MRSA in the UK and Ireland. It has already shown its value by investigating the incidence and transmission of the main US strain of MRSA in the East of England. A 2017 study also showed that transmission is not just attributable to large hospital outbreaks but can result from the accumulation of many unrecognised episodes.

2017: Developing a 3D system to better study TB

A multidisciplinary team from the University of Southampton and University College London develops a 3D system to enable researchers to better understand the bacteria that causes tuberculosis (TB). The system uses a technique known as electrostatic encapsulation to make tiny spheres of collagen – a connecting tissue in the body – within which human cells are infected with TB bacteria. The conditions more closely reflect events in patients than similar 2D techniques. 

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2017: How bacteria resist ‘last-resort’ antibiotic

An international team, led by the University of Bristol and part-funded by the MRC, discovers how the MCR-1 gene protects bacteria from ‘last-resort’ antibiotic colistin. Colistin is used to treat life-threatening bacterial infections that do not respond to other antibiotics. Colistin acts by binding to, and disrupting, a bacterium’s outer surface. However, bacteria carrying MCR-1 make a protein that modifies the bacterial surface, reducing colistin binding and making the organism resistant. The researchers hope that this finding will ultimately help identify routes to overcoming MCR-1 activity.

2017: Restricting use of common antibiotic cuts cases of C.difficile

A study by the University of Leeds and Public Health England finds that restricting the use of fluoroquinolone antibiotics was more effective than a high-profile hospital 'deep-clean' in reducing UK antibiotic-resistant Clostridium difficile. The study concluded that overusing these antibiotics led to the huge outbreak of C.difficile from 2006 onwards. This was because overuse killed non-resistant bacteria, allowing resistant C.difficile to thrive. Reducing fluoroquinolone use led to an 80 per cent fall in UK antibiotic-resistant C.difficile infections. These findings are important because other regions including North America do not restrict fluoroquinolone use and still experience epidemic numbers of C.difficile infections.

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