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Jon Davies on his PhD project and antibiotic resistance

20 December 2017

Stepping up the war on antibiotic resistance.

We have asked CDT researcher Jon Davies (2015 Cohort) to tell us more about his PhD project, following his Nature Communications paper that was picked up by the national press. He says:

"On a global scale there are few greater threats to human health than the rapid rise of antibiotic resistance. It is therefore important that we continue to discover and develop new antibiotics, preferably possessing unique modes of action.

One compound of particular interest is pleuromutilin, a naturally occurring antibiotic produced by certain types of mushroom. Interestingly, derivatives of pleuromutilin have been used in veterinary medicine for over 30 years without any evidence of significant resistance in their target bacteria.

In my PhD project I am looking to produce a range of new analogues of pleuromutilin, which will then be tested for their antibiotic properties.

To make these compounds we use a combination of chemistry and biology to modify a pleuromutilin-derived molecule called mutilin. The desired modifications are initially performed using organic synthesis, before a two-step biotransformation is used to complete the conversion to the potential antibiotic targets.

These biotransformations are performed using enzymes discovered in a pleuromutilin producing mushroom called Clitopilus passeckerianus.

Using this approach, I have been able to produce several new semi-synthetic pleuromutilin derivatives. Excitingly, one of these compounds has shown enhanced antibiotic activity."

Further information

See also "Mushrooms could hold key to new antibiotics", i Newspaper, 29 Nov. 2017 - By Padraic Flanagan

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