Key milestone towards the development of a new clinically useful antibiotic

July 12th 2010

Scientists have identified the genes necessary for making a highly potent and clinically unexploited antibiotic in the fight against multi-resistant pathogens.

“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 on the paper to be published in PNAS.

“Our study has allowed us to understand how the antibiotic is made by a bacterium that was first isolated from Indonesian soil. Now we can engineer the bacterium to make similar but better molecules, and lots of them.”

“For example, we can take rational approaches to improve its pharmacological properties, such as its stability in the blood stream and how it distributes into tissues.”

The producing bacterium, Microbispora corallina, is difficult to work with. It grows very slowly and no tools existed for its genetic manipulation. PhD student Lucy Foulston developed the tools herself. She then took advantage of new developments in genome sequencing to identify and then isolate the M. corallina gene cluster responsible for microbisporicin production.

This allowed her to analyse how the bacterium makes the molecule and the functions of the genes involved. Notably, she was able to identify 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.

“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 that 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.”

This research was funded by the Biotechnology and Biological Sciences Research Council (BBSRC), and the John Innes Centre is an institute of the BBSRC.
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Contacts

JIC Press Office
Zoe Dunford, Tel: 01603 255111, email: zoe.dunford@jic.ac.uk
Andrew Chapple, Tel: 01603 251490, email: andrew.chapple@jic.ac.uk

Notes to Editors

Reference: “Microbisporicin gene cluster reveals unusual features of lantibiotic biosynthesis in actinomycetes” Lucy C. Foulston and Mervyn J. Bibb will be published online by PNAS on Monday 12th July 2010 doi: 10.1073/pnas.1008285107

The John Innes Centre, www.jic.ac.uk, is an independent, world-leading research centre in plant and microbial sciences with over 800 staff. JIC is based on Norwich Research Park and carries out high quality fundamental, strategic and applied research to understand how plants and microbes work at the molecular, cellular and genetic levels. The JIC also trains scientists and students, collaborates with many other research laboratories and communicates its science to end-users and the general public. The JIC is grant-aided by the Biotechnology and Biological Sciences Research Council, www.bbsrc.ac.uk.

BBSRC is the UK funding agency for research in the life sciences. Sponsored by Government, BBSRC annually invests around £450 million in a wide range of research that makes a significant contribution to the quality of life in the UK and beyond and supports a number of important industrial stakeholders, including the agriculture, food, chemical, healthcare and pharmaceutical sectors. www.bbsrc.ac.uk

The commercial name for microbisporicin is NAI-107 and clinical development is being led by Italian and American companies.