‘Lantibiotics are antibiotic molecules produced by soil bacteria, and we are studying probably the most potent one known, microbisporicin, which is active against many different pathogens,’ said Professor Mervyn Bibb from the John Innes Centre, co-author of a paper to be published in Proceedings of the National Academy of Sciences (PNAS).
The study has allowed the scientists to understand how the antibiotic is made by a bacterium that was first isolated from Indonesian soil. The aim is to engineer the bacterium to make similar but better molecules, and many of them.
The producing bacterium, Microbispora corallina, is difficult to work with because it grows very slowly and no tools existed for its genetic manipulation. Lucy Foulston, a PhD student at the John Innes Centre, developed the tools herself. She then used genome sequencing to identify and isolate the M. corallina gene cluster responsible for microbisporicin production.
Foulston analysed how the bacterium makes the molecule and the functions of the genes involved. She also identified the genes responsible for giving microbisporicin some of its unique features.
The antibiotic molecule binds to a well-established target in the pathogenic bacteria it kills, and as yet there are no signs of resistance towards it.
Microbisporicin is very effective at killing disease-causing bacteria, including Clostridium difficile, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin resistant pathogens.
The commercial name for microbisporicin is NAI-107. Italian and American companies are leading its clinical development.
‘This molecule is already in late preclinical-phase trials and in animal models has shown to be more effective than the current drugs of last resort, linezolid and vancomycin,’ said Professor Bibb.
‘We believe this study will make a major contribution to the future clinical development of this exciting antibiotic, and the derivatives that can be made using the knowledge and technology that we have developed.’
The Biotechnology and Biological Sciences Research Council (BBSRC) funded the research, and the John Innes Centre is an institute of the BBSRC.
