Tackling antibiotic resistance

Antibiotic resistance is a major threat to the future development of humanity. Their inappropriate use has led to an alarming rise in treatment-resistant infections and in 2019 an estimated 1.27 million people died of formerly-preventable diseases. However, despite global acknowledgement of this crisis, only two new classes of antibiotics have been discovered within the last 50 years, not nearly enough to keep pace with the growing trend of resistance. The world is reaching a tipping point and urgently needs to invest in new antibiotic treatments to ensure simple infections remain treatable.

"Antibiotic resistance has severe consequences for both life expectancy and quality. The UK recorded increases in deaths from preventable diseases in the last 10 years, but antibiotic resistance also has implications for recovery from routine medical procedures, and for the global economy (through the cost of managing diseases and loss of workers)," explains Michael Macey, a microbiologist at The Open University. "Solutions to develop new antibiotics have been hindered by low discovery rates, the lengthy pathway to clinical approval, and a low success rate of potential antibiotic candidates."

Macey and an international team of collaborators are working to combat this resistance threat. As part of The Open University's Open Societal Challenges programme, the team will develop a method to screen microorganisms from some of the most extreme environments on Earth, searching for gene clusters or molecules that could lead to new antibiotics. Harsh conditions such as the extreme salinity of the Saharan salt flats, the high temperatures of Icelandic hot springs, or the extreme low temperatures of the Arctic give rise to some extraordinary microorganisms with unique adaptations to their hostile environment. The unusual biochemistry of these species, known as extremophiles, is a treasure trove for medicine, with hundreds of novel compounds exhibiting potent biological activity which could be developed into new medications.

"The vision is to develop a toolkit to identify novel antibiotics in extreme environments," says Macey "By screening genetic datasets from microbes in extreme environments, we hope to identify novel genes that encode for metabolites with possible antibiotic activity. Hopefully down the line this will lead to new effective antibiotic treatments reaching patients."

The Open University AstrobiologyOU group has an extensive database of genetic data from extreme environments all over the world and Macey's team will begin by mining this dataset for promising microbial candidates. Using complex bioinformatics programs to handle the data, the team will identify specific gene clusters associated with antibiotic activity. Each gene cluster encodes for a specific compound produced by the microbe and, by synthesising the promising gene sequences, the team will be able to identify and analyse these novel molecules. Each chemical candidate will then be evaluated against a panel of the most significant antibiotic-resistant strains of bacteria (known as the ESKAPE pathogens) and effective compounds will be progressed to the next stage of drug development.

"Antibiotic resistance is one of the biggest challenges we face today and we urgently need novel treatments," says Macey. "Extreme environments are a majorly underexplored resource for medicine and will be a vital tool for fighting this crisis."