The findings, to be published in PNAS, describe how Planomonospora alba, under conditions of mild nutrient starvation, can increase production of the antibiotic planosporicin. Specifically, initiation of a feed-forward mechanism results in release of a key regulatory protein required for high levels of planosporicin biosynthesis, an event which in turn favours its synchronous production in all cells of the colony.
Further to this discovery, scientists Dr Emma Sherwood and Professor Mervyn Bibb at the John Innes Centre were able to harness these underlying molecular mechanisms further to increase planosporicin production artificially, through manipulating regulatory genes controlling its expression. Crucially, planosporicin is similar to the antibiotic NAI-107 that is about to enter clinical trials for Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) infections. The knowledge gained from this study is thus being used to increase NAI-107 production, pointing to the possibility that adapting this technology towards production of other types of antibiotics may prove commercially beneficial.
Production of new antibiotics is no small problem, given that the number of multi-drug resistant (MDR) infections is increasing rapidly, as Chief Medical Officer Dame Sally Davies has repeatedly warned. The problem is compounded by the fact that due to the financial and technological issues surrounding their development, the antibiotic pipeline has reduced dramatically in recent years. This study therefore heralds an important development, as this technology may lead to easier methods of scaling up antibiotic production for commercialisation.
“We have shown for the first time that an antibiotic with clinical potential can act as signalling molecule to trigger its own synthesis,” said Professor Bibb.
“Our work shows with the right understanding it is possible to increase productivity very dramatically in a targeted and knowledge-based manner.”