Resensitising bacteria to old agents

With rising rates of antimicrobial resistance, one company, Blueberry Therapeutics, has been working on a way to give a new lease of life to old drugs, by re-sensitising them to the antibiotics we already do have, as Blueberry Co-founder, and former surgeon, Mike Davies explains to Chris Smith...

Chris -    So, you've decided to swap your scalpel for a sort of molecular scalpel in this instant.

Mike -   Indeed, yes. Well, we're Blueberry Therapeutics.  What we're doing, is to basically inhibit the resistance of resistant bacteria.  So, we effectively make them sensitive to current antibiotics, the ones that they have become resistant to. We do that with a very clever technique using a nanoparticle delivery.  We have a nanopolymer that basically wraps itself around certain things, certain drugs, certain proteins and things, and delivers them into the bacterial cells.  So, we have developed what are called aptamers and then specifically this area, something called an affimer which is really a tiny, tiny little antibody, really incredibly small, related to an antibody.  These are taken up by the nanopolymer into what's called a nanoparticle and effectively delivered into the bacterial cell.  We're targeting the way that those bacteria actually inhibit antibiotics.  There are  over 200 ways that bacteria inhibit antibiotics and stop them from working.  We're literally switching those off.

Chris -   So, what happens then if the bacteria mutate because one of the things that bacteria do is they change all the time.  So, why can't they just change to get around what you're throwing at them?

Mike -   Well, that's a very good question and of course, we will have to look for that as we develop these compounds, but first of all, they haven't done that before because there haven't been these ways of blocking really effectively the resistance mechanisms.  We can probably keep pace with that because we have these small proteins, that we call affimers, and they are literally a small number of amino acids - the things that build up proteins long.  And they're built like a tiny antibody as I say.  So, they've got two arms that we can change by one amino acid and it will literally change how it binds.  Now, with that process, the thought is, and it's a big picture for the future, but the thought is, as a bacterium or bacteria change and become resistant perhaps to one of our affimers, we can rapidly change it so we develop a new way of blocking the new resistance.

Chris -   So, if you're putting in something that is a protein though which is what your treatment is, is there not a danger that a person's immune system will react to that and then you'll get an immune response?  You'll make your own antibodies to your drug.

Mike -   Well, that's again a very, very good question and something that we would carefully look for in the development.  Although we we will start off by the topical delivery of these aptamers, so we'll start off in MRSA infected wounds, such as venous leg ulcers and diabetic foot ulcers.  And the affimers that we give are targeted directly at the bacteria.  We doubt if we will see an immune response.  We will have to look for that and it's a very important part of the drug development.