An antibiotic has been found to stimulate its own production. The findings, to be published in PNAS, could make it easier to scale up antibiotic production for commercialisation. Scientists Dr Emma Sherwood and Professor Mervyn Bibb from the John Innes Centre were able to use their discovery of how the antibiotic is naturally produced to markedly increase the level of production.
"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.
The antibiotic called planosporicin is produced by a soil bacterium called Planomonospora alba.
When nutrients become limited, a small amount of the antibiotic is
produced. The antibiotic is then able to trigger a mechanism which
coordinates its own production throughout the bacterial population
resulting in high levels.
"A frequent stumbling block in developing a natural product for
commercialisation is being able to provide enough material for clinical
trials," said Professor Bibb.
With knowledge of this signalling mechanism in hand, the scientists
were able to increase production by overexpressing two positively acting
regulatory genes and deleting one that acts negatively. 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 being used to increase NAI-107 production.
Commercial manufacturers of antibiotics may be able to use the
results to reduce production times and therefore reduce costs. Bacteria
often have to be grown for days and sometimes weeks before they start to
make effective amounts of an antibiotic. Sherwood and Bibb were able to
trigger production essentially from the beginning of growth.
The work was funded through JIC's core strategic grant from the Biotechnology and Biological Sciences Research Council.