Download Project Description

Role:
Research Fellow - Microbiology
Project Title:
A new pipeline of first in class antibiotics templated
on the bacteriocins
Grade:
7
Reports to:
Dr Mathew Upton
Project Description:
Antibiotic resistant bacteria kill over 25,000 people a year in Europe and threaten a
return to a time when minor infections can be fatal and routine surgery poses high
risks. With development pipelines empty, there is a critical need for novel therapies to
kill antibiotic resistant bacteria and serve as scaffolds for derivatisation, diversification
and enhancement of efficacy. We have discovered an exciting new peptide antibiotic
(bacteriocin) with potent activity against meticillin resistant Staphylococcus aureus
(MRSA) and other pathogenic bacteria. A single dose of the new antibiotic, epidermicin,
is more effective than six doses of the current therapy in a model of infection.
Epidermicin is part of an exciting new class of antimicrobials that have great potential
to prevent or treat bacterial infections. In this project, with a unique network of partners,
we will work with staff at the National Physical Laboratory using powerful structurefunction analysis tools to inform design of new peptides based on epidermicin and
other bacteriocins. These novel peptides will be tested against a wide range of
clinically relevant pathogens and characterised in detail. Promising candidates will be
progressed into commercially viable production systems using the world-leading
industrial biotechnology skills at Ingenza Ltd.
The project is funded by Innovate UK. Dr Upton’s group includes graduate and
postdoctoral researchers active in discovery, characterization and clinical
development of bacteriocins.
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Halliwell S, Warn P, Sattar A, Derrick JP, Upton M. A single dose of
epidermicin NI01 is sufficient to eradicate MRSA from the nares of cotton rats.
J Antimicrob Chemother, 2017. 72 (3): 778-781.

Gibreel TM, Upton M. Synthetic epidermicin NI01 can protect Galleria
mellonella larvae from infection with Staphylococcus aureus. J Antimicrob
Chemother. 2013. 68 (10):2269-73.

Sandiford S, Upton M. Identification, characterization, and recombinant
expression of epidermicin NI01, a novel unmodified bacteriocin produced by
Staphylococcus epidermidis that displays potent activity against
Staphylococci. Antimicrob Agents Chemother. 2012. 56 (3):1539-47.

Wescombe PA, Upton M, Renault P, Wirawan RE, Power D, Burton JP,
Chilcott CN, Tagg JR. Salivaricin 9, a new lantibiotic produced by
Streptococcus salivarius. Microbiology. 2011 May;157(Pt 5):1290-9.

Daly KM, Upton M, Sandiford SK, Draper LA, Wescombe PA, Jack RW,
O'Connor PM, Rossney A, Götz F, Hill C, Cotter PD, Ross RP, Tagg JR.
Production of the Bsa lantibiotic by community-acquired Staphylococcus
aureus strains. J Bacteriol. 2010 Feb;192(4):1131-42.
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