Resistance-busting antibiotics

New resistance-busting antibiotic combination discovered

A collaborative team, including many researchers from the Department of Chemistry, have discovered a new potential treatment that could extend the use of a class of ‘last-resort’ antibiotics called carbapenems in the face of antibiotic resistance.

Carbapenems are used to treat serious, multi-drug resistant infections such as sepsis, pneumonia, and urinary tract infections when other antibiotics like penicillin have failed. But some bacteria have found a way to survive treatment with carbapenems, producing enzymes called metallo-beta-lactamases (MBLs) that break down the carbapenem antibiotics and stop them from working.

Highly collaborative research, conducted by scientists from the Ineos Oxford Institute (IOI) for Antimicrobial Research at the University of Oxford (based in the Departments of Chemistry and Zoology) and several institutions across Europe, found that a new class of enzyme blockers, called indole carboxylates, can stop certain antibiotic-resistant enzymes from working. This leaves the antibiotic free to attack and kill bacteria such as E. coli in the lab and in infections in mice.

The new research, published in Nature Chemistry, was funded by the Innovative Medicines Initiative (IMI) through the European Lead Factory (ELF) and the European Gram-Negative Antibacterial Engine (ENABLE) programmes.

The World Health Organisation (WHO) estimates that by 2050, 10 million deaths will be due annually to antimicrobial resistance, overtaking the number of cancer related deaths and making it one of the most pressing health problems faced by humanity today.

Professor Christopher Schofield, Academic Lead (Chemistry), Ineos Oxford Institute at the University of Oxford, said:

An increase in antimicrobial resistance is absolutely inevitable. It a massive problem because collectively we haven’t been making enough new clinically useful antibiotics. As a society we must find ways both to make new antibiotics and protect the ones we have. The alternative is that routine modern medicine will be disrupted in a manner simply too horrendous to conceive.

The collaborative efforts of academics and industry scientists have discovered a brand-new class of drug that can shut down one of the ways bacteria fight back against antibiotics. This research is the culmination of years of work, from screening huge libraries of chemicals, through to testing the best drug candidates in pre-clinical studies in the lab. We are actively progressing this new drug type towards clinical trials in people, most importantly in lower- and middle-income countries where resistance to carbapenem antibiotics is widespread.