Breaking down antibiotic resistance
How does antibiotic resistance work?
Bacterial lung infections such as Pseudomonas aeruginosa and Staphylococcus aureus are common in people with cystic fibrosis. They lead to inflammation, lung damage and ultimately make it less easy to breathe. It can be hard to treat these infections as some strains are resistant to antibiotics.
Although it is well known that, over time, bacteria become resistant to these antibiotics, exactly how this happens is less well understood.
There are several ways that this can happen, such as through changes in bacterial cells’ outer structure and developing an ability to pump antibiotics out of their cells. These are the better-known channels of antimicrobial resistance that occur mainly in free living bacteria.
Another less well-known way in which antimicrobial resistance can be propagated is known as phenotypic resistance. This occurs when bacteria live and grow in communities that are known as biofilms. Bacteria that exist in biofilms behave differently to those that are free living. One of the differences is that they secrete a defensive layer that shields them from the effects of antibiotics and the body’s own immune system. This means that infections become persistent and considerably more difficult to eradicate.
One strategy to combat phenotypic resistance is to use two drugs together – an antibiotic and another drug to break up the biofilm, improving the chances of the antibiotic reaching its target. It is here where Neem’s work is shining a spotlight.
Researchers in Denmark have shown that ajoene can help break up the biofilm of bacteria, opening the door for antibiotics to become effective again. Chemicals that work alongside antibiotics to improve their effectiveness are known as ‘antibiotic resistance breakers’ or ‘adjuvant therapies’.
Neem Biotech, which is matching the Trust’s £100,000 funding, is developing a new antibiotic resistance breaker, using ajoene as a starting point. The team will be fine tuning its chemical properties to enhance its biological activity.
Neem is able to produce a variant of ajoene synthetically. This is key to ensuring that it meets international pharmaceutical drug development standards and is acceptable to drug development regulators such as the FDA and EMA.
The balancing act of drug design
The design of new drugs is a delicate balance between keeping the beneficial effects that researchers first noticed, and refining the chemistry to ensure: the effects are long lasting, the potential for side effects is reduced and the drug is practical and economic to produce.
For every slight change made to the chemistry to increase the drug’s stability, the potential impact on its beneficial effects need to be checked again. Neem Biotech will be looking at the potential of a series of lab-made chemical variants of this antibiotic resistance breaker, testing them in a range of experiments in the lab. At the end of the study the researchers will have narrowed down which of these variants can be investigated as a potential adjuvant therapy for treating P. aeruginosa or S. aureus in people with cystic fibrosis.
Graham Dixon, Chief Executive Officer of Neem Biotech, said: “Neem is delighted to receive this grant. We see the opportunity to work with the UK Cystic Fibrosis Trust to develop a safe and effective treatment regime to manage persistent bacterial lung infections in people with cystic fibrosis as a real opportunity to make a tangible difference to the lives of people living with cystic fibrosis.”
Paula Sommer, Head of Strategic Innovation at the UK Cystic Fibrosis Trust, said: “As the only UK charity that funds medical research into cystic fibrosis, it will be great to work with Neem Biotech on this paradigm changing project.
“Antimicrobial drug development is key to helping people with cystic fibrosis as bacterial lung infections cause severe lung damage and impede lung function which is one of the biggest causes of death for people with the condition.”