Development of epidermicin NI01 for nasal decolonization
Lead Research Organisation:
University of Manchester
Department Name: Medical and Human Sciences
Abstract
The World Health Organisation have stated that infections caused by antibiotic resistant bacteria (e.g. MRSA) are one of the greatest current threats to public health and there is an urgent need for novel antibiotics to combat drug resistant infections. We have discovered epidermicin, an exciting and important new antibiotic that rapidly kills MRSA and other bacteria. The new antibiotic is more active than current antibiotics, is non-toxic and bacteria don't develop resistance to it. These are significant advantages over current antibiotics so we plan to develop epidermicin for clinical use. People who carry MRSA in the nose have a high risk of developing infection and transmitting MRSA, so we will examine how effective epidermicin is for removing MRSA from the nose. We will also carry out experiments designed to help us to understand how epidermicin kills bacteria and why they do not become resistant and carry out work to ensure that the antibiotic is not toxic when used clinically.
Publications
Hammond K
(2021)
Atomic force microscopy to elucidate how peptides disrupt membranes.
in Biochimica et biophysica acta. Biomembranes
Hammond K
(2020)
Flowering Poration-A Synergistic Multi-Mode Antibacterial Mechanism by a Bacteriocin Fold.
in iScience
Morra R
(2016)
Dual transcriptional-translational cascade permits cellular level tuneable expression control.
in Nucleic acids research
Halliwell S
(2017)
A single dose of epidermicin NI01 is sufficient to eradicate MRSA from the nares of cotton rats.
in The Journal of antimicrobial chemotherapy
| Description | Demonstrated in a relevant model that epidermicin is better than the current therapy for preventing infection with methicillin resistant S aureus (MRSA), on of the most important pathogens seen in healthcare settings. Determined the structure of epidermicin. Identified novel data that supported submission (March 2014) of a second patent application protecting the technology being developed. |
| Exploitation Route | In vivo data justify further development through the pre-clinical pathway towards nasal decolonisation, to prepare epidermicin for use in a Phase I clinical trial |
| Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |
| Description | Findings from this work have been communicated to audiences in the general public (science in the news event and University of the 3rd Age meetings and in various local and national media outlets. The findings have been well received and generated interest in these settings. |
| First Year Of Impact | 2013 |
| Sector | Healthcare |
| Impact Types | Societal |
| Description | Capital equipment for AMR research |
| Amount | £142,000 (GBP) |
| Funding ID | 86184-540263 |
| Organisation | Innovate UK |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2017 |
| End | 03/2017 |
| Description | Health and Life Sciences call |
| Amount | £933,000 (GBP) |
| Funding ID | TS/R008396/1 |
| Organisation | Innovate UK |
| Sector | Public |
| Country | United Kingdom |
| Start | 08/2017 |
| End | 07/2020 |
| Description | Industrial Biotechnology Catalyst - Industry Research award |
| Amount | £417,092 (GBP) |
| Funding ID | 44921-302214 |
| Organisation | Innovate UK |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2015 |
| End | 03/2017 |
| Description | Pre-clinical validation of a potent candidate in the fight against AMR HCAI |
| Amount | £1,182,041 (GBP) |
| Funding ID | 971631 |
| Organisation | Innovate UK |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2019 |
| End | 01/2021 |
| Description | SfAM PhD |
| Amount | £67,000 (GBP) |
| Organisation | Society for Applied Microbiology |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 10/2017 |
| End | 09/2020 |
| Description | Development of expression system for commercial scale production |
| Organisation | Ingenza Ltd |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Ingenza have partnered with us to develop the recombinant expression system for production of epidermicin and related peptides. This work is now supported by a TSB/Innovate UK IBC award (starting April 2015). My research team will be evaluating the peptides that are produced in the Ingenza expression pipeline. |
| Collaborator Contribution | Ingenza are bringing 14 years of IB expertise to the project to maximise the chance of successfully achieving our target level of expression |
| Impact | None yet |
| Start Year | 2014 |
| Description | Mode of action work with Leeds University |
| Organisation | University of Leeds |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Peptide supplied to Alex O'Neill who worked with Post-doc on project and his own PhD student to investigate the mode of action |
| Collaborator Contribution | Investigated the mode of action using liposomes and in house strains of bacteria to indicate cell wall activity of peptide. Also mapped the cellular response at the level of macromolecular synthesis |
| Impact | Poster presentation at ICAAC, 2013. This work is being written up into a manuscript for submission in the near future |
| Start Year | 2012 |
| Description | National Physical Laboratory/IBM for creation of novel antimicrobials based on epidermicin |
| Organisation | National Physical Laboratory |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | This is part of a new Innovate UK funded project with NPL, the University of Plymouth and Ingenza Ltd. Our role in the project is to guide design of new antimicrobials based on epidermicin and investigate the activity of variants. This will include assessment of spectrum of antimicrobial activity against clinically relevant bacteria and investigation of toxicity of novel antimicrobials. |
| Collaborator Contribution | Max Ryadnov at NPL has been working with colleagues at IBM Hartree to develop novel epidermicin variants, using cognitive computing. The NPL/IBM approaches will provide new sequence variants that will be investigated in silico at IBM. Promising molecules will be synthesised at NPL and initial bioactivity assessments will be carried out. Promising candidates will be passed to my group for further testing (above). Any candidates worth progressing to larger scale evaluation will be passed to Ingenza for recombinant expression process development and scaleup. |
| Impact | This collaboration was cemented and current work facilitated by an award from Innovate UK (Health and Life Sciences award) |
| Start Year | 2017 |
| Description | Pseudo-allergenic activity of epidermicin NI01 |
| Organisation | RefLab |
| Country | Denmark |
| Sector | Private |
| PI Contribution | We provided NI01 peptide to the collaboration and some costs (€1200) for analysis probes were paid for by Amprologix, the University of Plymouth spinout that is commercialising NI01 |
| Collaborator Contribution | Michelle Vang was a staff member working on NI01 and she moved to RefLab in 2020 and then established a collaboration with us and proposed the work with NI01 in a model of human ex-vivo skin to examine pseudo-allergic responses to the peptide NI01. |
| Impact | None yet |
| Start Year | 2020 |
| Description | Wound healing activity of epidermcin |
| Organisation | Roskilde University |
| Country | Denmark |
| Sector | Academic/University |
| PI Contribution | Discussions we held at the International Antimicrobial Peptide meeting in Leiptzig, Germany in August 2016 about using epidermicin in Havard Jenssen's wound healing assays. An MTA was put in place and epidermicin was sent to Roskilde for use in assays. |
| Collaborator Contribution | The epidermicin provided was used in wound healing and preliminary cytokine assays |
| Impact | An out line patent application has been submitted based on this work and Michelle Vang from Havard Jenssen's group is planning a 3 month visit to the UK to work in my lab to develop the data set further, to support a future grant application. |
| Start Year | 2017 |
| Title | NOVEL ANTIMICROBIAL PEPTIDES |
| Description | The present invention provides novel antimicrobial peptides and nucleic acids encoding them, the peptides having an inhibitory or bactericidal/bacteriostatic effect on both Gram- negative and Gram-positive bacteria. The invention includes methods of treating bacterial infections and preventing the spread of the infections or contamination by the infection. The peptides of the present invention are of particular use as therapeutics to treat Gram- negative infections and are of use in impregnation, covering or coating medical devices or implants or prosthetics prior to introduction into a patient's body |
| IP Reference | WO2015132572 |
| Protection | Patent application published |
| Year Protection Granted | 2015 |
| Licensed | No |
| Impact | None yet |
| Title | Epidermicin |
| Description | Pre-clinical development of epidermicin towards use in nasal decolonisation for MRSA carriage - during the FoF project we obtained excellent in vivo data in a murine model relevant to the selected clinical indication. This has supported further funding applications to facilitate development of epidermicin towards clinical trials |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Refinement. Non-clinical |
| Year Development Stage Completed | 2014 |
| Development Status | Under active development/distribution |
| Impact | We solved the crystal structure of epidermicin. This will inform future development and inform our efforts to understand the mode of action. |
| Company Name | AMPROLOGIX LIMITED |
| Description | A University of Plymouth spin out established to commercialize epidermicin IPR arising from work in University of Manchester and University of Plymouth. |
| Year Established | 2018 |
| Impact | Shortly after company formation, an award was made from the Department of Health and Social Care (via Innovate UK/SBRI) for a contract valued at £12.m to progress the lead compound (epidermicin) through pre-clinical development. |
| Description | Haliwell paper Press Release |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | A press release was issued by the University of Plymouth in February 2017 to promote the publication of a paper describing unique and potent activity of epidermicin in an animal infection model. This release was picked up locally by Radio Devon featuring on the local eveing news (http://www.bbc.co.uk/news/live/uk-england-devon-38929340). A number of phone calls were taken as follow up to the release. |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://www.bbc.co.uk/news/live/uk-england-devon-38929340 |
| Description | Opinion piece in local print news |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Opinion piece drafted and submitted to regular media outlets. This article aimed to increase awareness about antibiotic resistance during World Antibiotic Awareness week in November 2017 and mentioned briefly the work in my group developing new antibiotics. The story was picked up by the Cornish Times and I was subsequently approached by the Mail on Sunday for comment and input into a short piece on the health related importance of marine environments (this was around the time BBC were showing the Blue Planet series. |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://www.cornish-times.co.uk/article.cfm?id=112541&headline=World%20Antibiotic%20Awareness%20Week&... |
| Description | Press release on company formation |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | A press release from the University of Plymouth was made to publicize the formation of Amprologix Ltd. This was coordinated with releases from Ingenza (industrial partners) and a 'reach' article by Frontier IP ltd, the University of Plymouth commercialisation partners, who have an equity share in Amprologix. This story was picked up by various local media outlets and international business sites. The release and a subsequent one about award of an SBRI contract (971631) generated interest in academic an industry quarters and resulted in invites to present at Bioinfect, Manchester Nov 2018 and the conference on Novel Antimicrobials and AMR Diagnostics, Berlin, March 2019. It also resulted in many offers of service provision etc to assist with company development or R&D. Examples of relevant sites referencing the original release - https://cen.acs.org/pharmaceuticals/antibiotics/UK-antibiotics-firm-Amprologix-launches/96/i39 http://www.pharmtech.com/amprologix-ingenza-get-funding-antibiotic-development https://www.bloomberg.com/research/stocks/private/snapshot.asp?privcapId=588605641 |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.plymouth.ac.uk/news/university-spinout-company-to-develop-new-antibiotics |
| Description | TEDx Talk |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Based on my expertise and profile in antibiotic resistance and discovery (from UKRI funded research), I was invited to present a TEDx talk. This talk has now had nearly 2000 views on Youtube since January 2019. |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.youtube.com/watch?v=makV286ZFDk&t=11s |