New research findings offer new hope in fight to rescue antibiotic of last resort

21 May 2017

Second research paper offers encouraging hope

New research published this month in the journal Biochimica et Biophysica Acta has confirmed a significant leap forward in the global fight against antibiotic resistance.

The new study complements, and indeed strengthens, last month’s findings released in April’s Nature’s Scientific Reports which highlighted how some superbugs, including MRSA, which causes septicaemia, meningitis and some other hospital-acquired infections, can become resistant to one of the key antibiotics of last resort.

The breakthrough discoveries were found by researchers at the University of Central Lancashire (UCLan), the University of Nottingham and the Diamond Light Source in Oxfordshire.

The studies show that a specific protein, known as VanS, interacts directly with Vancomycin – one of the antibiotics of last resort. The research also determined the strength with which the antibiotic binds and crucially this was shown to be weak.

These discoveries offers new insight into the mechanisms involved in activating resistance genes in some of the most difficult-to-treat and deadly infections, including penicillin-resistant pneumonia and MRSA, one of the most serious hospital-acquired infections.

"Understanding how these ‘resistance triggering’ mechanisms work in bacteria means that we can find new ways of destroying them, taking us one step closer towards combating these harmful superbugs."

‘Antibiotics of last resort’ are used to tackle serious and multi-drug-resistant infections

when other potential treatments have failed. Since some bacterial strains are now also evolving to become resistant to this last line of defence, fundamental research which addresses how this antibiotic resistance is triggered is crucial to address this global issue.

It is estimated that antimicrobial resistance, which renders existing antibiotics useless against some bacterial infections, will lead to the loss of 10 million lives a year by 2050 and cost £69tn per year globally. This is according to the Reviews on Antimicrobial Resistance published in 2016*, which highlights the severity of the issue.

Dr Mary Phillips-Jones, director of the studies and Senior Lecturer in Biochemistry and Microbiology at UCLan, said: “We’ve previously identified that the important antibiotic known as Vancomycin binds directly to a specific protein in the membrane of some key bacteria. We believe this may trigger the resistance mechanism, most likely in combination with other additional factors. In our new study we now also know that the interaction is weak, which offers new possibilities for finding drugs that bind more strongly.”

“Understanding how these ‘resistance triggering’ mechanisms work in bacteria means that we can find new ways of destroying them, taking us one step closer towards combating these harmful superbugs.”

"Identifying the key interaction point is a major step in helping us to permanently outwit them."

Stephen Harding, co-director of the study and professor of applied biochemistry at the University of Nottingham said: “Many bacteria are very clever in quickly adapting to defend against the medicines used to kill them. Identifying the key interaction point is a major step in helping us to permanently outwit them.”

The work utilised facilities made available at the University of Leeds and supported financially by the School of Pharmacy and Biomedical Sciences at the University of Central Lancashire, the National Centre for Macromolecular Hydrodynamics at the University of Nottingham and the Diamond Light Source.

Articles:

http://www.sciencedirect.com/science/article/pii/S0304416517301630

*The Review on Antimicrobial Resistance – Tackling Drug-Resistant Infections Globally: final report and recommendations

https://amr-review.org/sites/default/files/160525_Final%20paper_with%20cover.pdf