North West scientists select candidate in fightback against deadly superbugs

Dr Peter Jackson

A key research programme in Cheshire has identified a possible candidate to help in the fight against superbugs.

The AMR Centre (AMRC) in Alderley Park is leading the UK response to the global health crisis posed by our diminishing supply of effective antibiotics.

And it has selected a project to enter pre-clinical trials to tackle a range of superbugs.

The result of two years’ research, AMRC scientists have developed a new molecule that aims to restore the function of some existing antibiotics which have lost effectiveness as bacteria have evolved to render the drugs useless.

The new programme, known as the MBL inhibitor (MBLI), targets a range of enzymes that make bacteria resistant to penicillin and other widely-used beta-lactam antibiotics – in this case NDM-1 and other metallo-β-lactamases enzymes.

The problem enzymes disable the ability of an antibiotic to kill bacteria and, unusually, this resistance mechanism is easily transferable from one species of bacteria to another.

Bacteria containing NDM-1 have already caused significant fatalities and the spread of this enzyme has the potential to greatly diminish the number of treatment options for organisms such as E. coli and Klebsiella pneumoniae.

First identified in 2008 in New Delhi, NDM-1 has since been detected in bacteria in Pakistan, Sweden, the UK, the US, Canada, and Japan.

The goal is a treatment that could be given alongside existing antibiotics, blocking the resistance mechanism.

AMRC’s executive director, Dr Peter Jackson, said: “We are delighted to have reached this milestone.

“It’s the first programme from the AMR Centre portfolio that we have taken all the way from early stage research to nomination of a pre-clinical development candidate.

“There are now hundreds of cases of infection in the UK, rising from zero over the last five years. In some areas of India and China, the problem is already endemic and there’s a big pool of MBL-producing bacteria waiting to come our way.

“Our mission is to overcome resistance mechanisms and develop new treatments for serious infections.

“Our MBL inhibitor will be one of the first and, we hope, most effective broad-spectrum therapies against the emerging class of superbugs coming out of India and China.”

He added: “We’ve got 12 months of work to do now to confirm that the new drug is safe for use in humans, to support our first clinical trials in late 2020.”

Drug-resistant infections currently claim at least 700,000 lives, but the UK Government’s own review, led by Lord Jim O’Neill, predicts that by 2050 it will account for more than 10 million deaths per year worldwide, more than currently die from cancer.

And by 2050, if no new antibiotics are developed, the impact on the global economy will be 100 trillion dollars.

Antimicrobial resistance (AMR) is Darwinism in action: Common microbes that cause infectious disease are evolving so that they are no longer susceptible to the antibiotics that doctors have relied on for decades to treat their patients.

Without a new generation of antibiotics, many routine procedures will become life-threatening, from caesarean sections and hip replacements to cancer chemotherapy and heart transplants.

Despite the scale of the problem, there has been a market failure to develop new antibiotics – most of the major pharmaceutical companies have pulled out of antibiotics research, instead focusing on more lucrative sectors, such as cardiovascular disease and cancer.