Activity: Participating in or organising an event types › Key-note speaker and plenary lectures at conferences
We have evaluated a collection of 49 novel synthetic antibiotic compounds (sMGBs), which draw inspiration from natural products such as distamycin - that have the intrinsic ability to bind to the minor groove of DNA. Some of these compounds are active against Gram-positive pathogens including Clostridium difficile, and Staphylococcus aureus (including MRSA), at comparable levels of activity to vancomycin. There is a good structure-activity relationship and resistance to sMGBs has not been an issue in these target organisms.
sMGBs appeared less effective against Gram-negatives such as Pseudomonas aeruginosa. However, efficacy improved considerably in the presence of an efflux pump inhibitor. We have screened over 20 efflux pump mutants in order to identify the relative contributions of different drug efflux systems. Certain efflux mutants exhibited only 10% growth relative to the wild type P. aeruginosa strain, demonstrating selectivity between pump and sMGB substrate and we are currently exploiting this information so that we can design better anti-pseudomonas drugs. We are also actively investigating the mode of action against MRSA using a variety of next-generation sequencing approaches.