Unravelling the details of antibiotic function
A team involving Professor Colin Fishwick and Dr Katie Simmons have described the detailed mechanism of operation of the antibiotic cycloserine.
In a paper published in Nature Communications, the team describe how a combination of structural molecular biology, molecular modelling and microbiology was used to uncover the unique mechanism of binding of cycloserine to one of its target enzymes within bacteria, D-Ala-D-Ala ligase. The work has revealed that this antibiotic works via initially becoming phosphorylated within the bacterial cell, and it is the phosphorylated form of cycloserine that actually inhibits the bacterial enzyme and therefore ultimately behaves as an antibiotic.
The team’s findings are important as there is now an urgent need to identify new ways to combat the spread of bacteria that are resistant to currently used antibiotics, and may point the way to future novel approaches.