Bacterial evolution of antibiotic arsenals provides new drug blueprints

Scientists from Trinity College Dublin have discovered that two very different species of bacteria have evolved distinct, powerful antibiotic arsenals for use in the war against their bacterial neighbours.

By blueprinting precisely how the antibiotics function against methicillin-resistant Staphylococcus aureus (MRSA), the scientists have provided new options for drug designers seeking to hold back the global threat that antimicrobial resistance poses humanity.

Failure to develop effective antibiotics that counter resistance to current drugs will have disastrous consequences. It is estimated that by mid-century, just 30 years from now, antimicrobial resistance will result in a global death rate of up to 10 million per year. By 2030, the World Bank puts the cost of resistance at US$3.4 trillion in global gross domestic product. The need for new and effective therapeutics is immediate and immense.

The hope is that the basic research into the workings of an enzyme involved in bacterial coat synthesis reported in this article will contribute to the development of these urgently needed medicines.

While it is important from a purely scientific perspective to understand how nature crafts and moulds at the molecular level, as illustrated in this work, the scientists findings have the added benefit of providing drug designers chemical blueprints -- or pharmacaphores, which explain how a molecular structure lends itself to a specific action, such as an antibiotic effect -- which are known to work for bacteria in the real world.

These blueprints can now be used to guide pharmaceutical chemists when they design new, more effective drugs that are urgently needed in light of the accelerating global threat of antimicrobial resistance.

See:

Samir Olatunji, Xiaoxiao Yu, Jonathan Bailey, Chia-Ying Huang, Marta Zapotoczna, Katherine Bowen, Maja Remškar, Rolf Müller, Eoin M. Scanlan, Joan A. Geoghegan, Vincent Olieric, Martin Caffrey. Structures of lipoprotein signal peptidase II from Staphylococcus aureus complexed with antibiotics globomycin and myxovirescin. Nature Communications, 2020; 11 (1) DOI: 10.1038/s41467-019-13724-y

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)