Beyond Antibiotics
Lead Research Organisation:
University of Oxford
Department Name: Engineering Science
Abstract
The 2019 World Health Organisation (WHO) report on Antimicrobial Resistance (AMR) identifies it as: "one of the greatest threats we face as a global community." The evolution of drug-resistant bacteria, our over-use of antibiotics and failure to develop new methods for tackling infection could leave us without viable treatments for even the most trivial infections within the next 3 decades. There have been significant efforts by the WHO and national agencies to raise awareness of AMR and reduce the use of antibiotics, but there is still an urgent need to intensify these efforts and, crucially, to develop alternatives. The aim of the programme is to address this need.
The programme will consist of 4 interlinked work packages focussed on the core research objectives:
(1) The development of human organoid models for studying interactions between bacteria and the tissue microenvironment and larger scale interactions with the host microbiome.
(2) New microscopy methods to complement the organoid models and to facilitate rapid characterisation of bacteria for improved diagnosis.
(3) New antimicrobial therapeutics and targeted delivery techniques to improve the use of existing antibiotics and provide viable alternatives.
(4) "Drug-free" methods for treating infections and promoting immune function thereby further reducing the use of antibiotics and providing methods suitable for large scale environmental/industrial use.
These will be supported by 2 parallel translational activities to enable development of the translational pathway and wider engagement with clinical and industrial stakeholders, policy-makers and the public.
The programme will consist of 4 interlinked work packages focussed on the core research objectives:
(1) The development of human organoid models for studying interactions between bacteria and the tissue microenvironment and larger scale interactions with the host microbiome.
(2) New microscopy methods to complement the organoid models and to facilitate rapid characterisation of bacteria for improved diagnosis.
(3) New antimicrobial therapeutics and targeted delivery techniques to improve the use of existing antibiotics and provide viable alternatives.
(4) "Drug-free" methods for treating infections and promoting immune function thereby further reducing the use of antibiotics and providing methods suitable for large scale environmental/industrial use.
These will be supported by 2 parallel translational activities to enable development of the translational pathway and wider engagement with clinical and industrial stakeholders, policy-makers and the public.
Organisations
- University of Oxford (Lead Research Organisation)
- UNIVERSITY OF EXETER (Collaboration)
- University of Otago (Collaboration)
- UNIVERSITY OF BRITISH COLUMBIA (Collaboration)
- Oxford NanoImaging (Project Partner)
- National Biofilms Innovation Centre (Project Partner)
- Philips (Netherlands) (Project Partner)
- GlaxoSmithKline (United Kingdom) (Project Partner)
- Public Health England (Project Partner)
- Norbrook (United Kingdom) (Project Partner)
- Smith & Nephew plc (UK) (Project Partner)
- Boston Scientific (United States) (Project Partner)
- Karl Storz (Germany) (Project Partner)
Publications
Murray B
(2021)
Recurrent Urinary Tract Infection: A Mystery in Search of Better Model Systems
in Frontiers in Cellular and Infection Microbiology
Von Kügelgen A
(2022)
A multidomain connector links the outer membrane and cell wall in phylogenetically deep-branching bacteria
in Proceedings of the National Academy of Sciences
Böhning J
(2022)
Compressed sensing for electron cryotomography and high-resolution subtomogram averaging of biological specimens.
in Structure (London, England : 1993)
LuTheryn G
(2022)
Bactericidal and anti-biofilm effects of uncharged and cationic ultrasound-responsive nitric oxide microbubbles on Pseudomonas aeruginosa biofilms.
in Frontiers in cellular and infection microbiology
Esser T
(2022)
Cryo-EM samples of gas-phase purified protein assemblies using native electrospray ion-beam deposition
in Faraday Discussions
Plazonic, F
(2022)
Bactericidal effect of ultrasound-responsive microbubbles and sub-inhibitory gentamicin against Pseudomonas aeruginosa biofilms on substrates with differing acoustic impedance
in Ultrasound in Medicine & Biology
Plazonic F
(2022)
Bactericidal Effect of Ultrasound-Responsive Microbubbles and Sub-inhibitory Gentamicin against Pseudomonas aeruginosa Biofilms on Substrates With Differing Acoustic Impedance.
in Ultrasound in medicine & biology
Krause S
(2022)
The importance of biofilm formation for cultivation of a Micrarchaeon and its interactions with its Thermoplasmatales host.
in Nature communications
De Grandi D
(2022)
Facile production of quercetin nanoparticles using 3D printed centrifugal flow reactors.
in RSC advances
Herdman M
(2022)
High-resolution mapping of metal ions reveals principles of surface layer assembly in Caulobacter crescentus cells.
in Structure (London, England : 1993)
Jafari NV
(2022)
The urothelium: a multi-faceted barrier against a harsh environment.
in Mucosal immunology
Chun ALM
(2022)
Early biofilm and streamer formation is mediated by wall shear stress and surface wettability: A multifactorial microfluidic study.
in MicrobiologyOpen
Flores C
(2023)
A human urothelial microtissue model reveals shared colonization and survival strategies between uropathogens and commensals.
in Science advances
Choi V
(2023)
Drug delivery strategies for antibiofilm therapy.
in Nature reviews. Microbiology
Sathiananthamoorthy S
(2023)
Application of Various Techniques to Gain Insights Into the Complex Urinary Tract Microbial Communities of Renal Transplant Recipients.
in Transplantation direct
Morris CJ
(2023)
Effective Treatments of UTI-Is Intravesical Therapy the Future?
in Pathogens (Basel, Switzerland)
Lasri Doukkali A
(2023)
A hybrid individual-based mathematical model to study bladder infections
in Frontiers in Applied Mathematics and Statistics
LuTheryn G
(2023)
Cationic Microbubbles for Non-Selective Binding of Cavitation Nuclei to Bacterial Biofilms.
in Pharmaceutics
Böhning J
(2024)
The role of filamentous matrix molecules in shaping the architecture and emergent properties of bacterial biofilms.
in The Biochemical journal
Choi, V.
Drug delivery strategies for antibiofilm therapy
in Nature Reviews Microbiology
Description | Dr Gareth LuTheryn led small discussion Labour Shadow Secretary of State for Education, Bridget Phillipson, on antimicrobial resistance |
Geographic Reach | National |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | Prof. Dario Carugo participated in the National Biofilms Innovation Centre (NBIC) led workshop, titled "Biofilm Prevention." |
Geographic Reach | National |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Improvements to prevention of early-stage microbial adhesion and colonisation events at surfaces and interfaces, and curtailing the development and maturation of early-stage biofilms. |
Description | Prof. Dario Carugo's research was featured International Society for Therapeutic Ultrasound's Webinar "Sonobactericide for Treating Bacterial Infections" given by Dr Klazina Kooiman |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Increased knowledge of cutting edge scientific techniques that address the current shortage of effective antibiotics and antimicrobials. |
URL | https://istu.org/istu-live/istu-live-april-28-2022/ |
Description | Prof. Eleanor Stride contributed to National Engineering Policy Centre |
Geographic Reach | National |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | Prof. Eleanor Stride responded to the Department of Health and Social Care's consultation on antimicrobial resistance |
Geographic Reach | National |
Policy Influence Type | Contribution to a national consultation/review |
URL | https://www.gov.uk/government/consultations/antimicrobial-resistance-national-action-plan-call-for-e... |
Description | New collaboration set up between Prof. Eleanor Stride and Otago University, New Zealand |
Organisation | University of Otago |
Country | New Zealand |
Sector | Academic/University |
PI Contribution | New research partnership developed to facilitate the investigation of nitric oxide generating particles. This collaboration will leverage the impact biofilm disruption activities of the programme grant to more comprehensively address antimicrobial resistance without requiring additional resources. |
Collaborator Contribution | Access to laboratory facilities and knowledge around particle development processes. |
Impact | Improved research processes, as well as time and resource savings. |
Start Year | 2021 |
Description | University of British Columbia |
Organisation | University of British Columbia |
Department | UBC/BC Cancer Agency |
Country | Canada |
Sector | Academic/University |
PI Contribution | Novel delivery system for antibiotics |
Collaborator Contribution | Disease model for urinary tract infection |
Impact | none yet, experiments underway |
Start Year | 2022 |
Description | University of Exeter |
Organisation | University of Exeter |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Ultrasound system to enhance therapeutic agent delivery |
Collaborator Contribution | Provision of antibiotic virus particles |
Impact | experiments ongoing |
Start Year | 2021 |
Description | Beyond Antibiotics Programme Grant Twitter social media channel established |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Beyond Antibiotics Programme Grant social media channel established on Twitter. Followers grown to 818, with 191 posts published, and 105,075 Tweet impressions generated since the grant's start date on October 1st, 2021. |
Year(s) Of Engagement Activity | 2021,2022,2023 |
URL | https://twitter.com/AMR_Research |
Description | Beyond Antibiotics Programme Grant website developed |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Website developed to showcase the research of the Beyond Antibiotics Programme Grant and simultaneously raise awareness of antimicrobial resistance. |
Year(s) Of Engagement Activity | 2021,2022,2023 |
URL | https://beyondantibiotics.ox.ac.uk/ |
Description | Dr Ffion Hammond hosted an outreach stand at the ATOM Festival of Science and Technology, in Abingdon-on-Thames, Oxfordshire |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | The ATOM Festival of Science and Technology was held in Abingdon-on-Thames on Saturday 11th March from 9:30 to15:00. Dr Ffion Hammond hosted an outreach stall in collaboration with the Nuffield Dept of Orthopaedics Rheumatology and Musculoskeletal Sciences at the University of Oxford's "The Gut Florists" group. This outreach activity was aimed at families and focused on the subject of bacteria and the microbiome in health and disease. The activity was to make a bacterial pom pom out of differently coloured wool, as well as having bacteria trivia questions to vote on. Whilst focusing on the microbiome, a key angle of this was how the gut microbiome is affected by antibiotics (loss of 'good' bacteria) and how this impacts health, and how some bacteria can resist antibiotics (allowing 'bad' bacteria to grow and cause infection). |
Year(s) Of Engagement Activity | 2023 |
Description | Dr Gareth LuTheryn Presented at the 27th European Symposium on Ultrasound Contrast Imaging |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Conference presentation on antimicrobial and antibiofilm agents at 27th European Symposium on Ultrasound Contrast Imaging, which raised awareness of the importance of addressing biofilm disruption and dispersion as a mechanical way to increase the effectiveness of existing antimicrobial agents. |
Year(s) Of Engagement Activity | 2022 |
Description | Dr Gareth LuTheryn conducted 30 hours of KS4 and KS5 outreach on impacts of biofilms and antimicrobial resistance on public health |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Dr Gareth LuTheryn conducted antimicrobial resistance (AMR) tutorials for KS5 with UTC Norwich (Online). In addition, KS4 tutorials with Dormers Wells School (Southall), and KS4 tutorials with Sir William Ramsay School were delivered for a combined total of 30 hours of tutorial content. Tutorials focused on biofilms, infection and AMR, as well as how they impact public health. Tutorials were followed by a literature research project on how we can use new treatments and technologies as interventions for these chronic infections. |
Year(s) Of Engagement Activity | 2023 |
Description | Dr Gareth LuTheryn conducted KS3 and KS4 outreach in partnership with The Brilliant Club |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Introduction of the scientific research methodology and the issues associated with antimicrobial resistance and biofilms for human health. Raising awareness of the importance of antimicrobial stewardship and impacts of resistance on human health. |
Year(s) Of Engagement Activity | 2022 |
Description | Dr Gareth LuTheryn conducted Outreach and engagement with KS3 pupils at Livingstone Academy Bournemouth |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Outreach and engagement with KS3 pupils at Livingstone Academy Bournemouth on antimicrobial resistance and antibiotic development. The process and challenges affecting new antibiotic developments were disucssed. |
Year(s) Of Engagement Activity | 2022 |
Description | Dr Gareth LuTheryn conducted delivered KS4 tutorials |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Dr Gareth LuTheryn delivered a series of tutorials to KS4 students on antimicrobial resistance and antimicrobial drug delivery tutorials at Wexham School, Slough. Over the course of 5 weeks, 10 hours of tutorials were delivered reaching 14 Students and their parents. |
Year(s) Of Engagement Activity | 2023 |
Description | Dr Gareth LuTheryn delivered 10 hours of Tutorials with KS4 students at Springfield School, Portsmouth |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Delivered 10 hours of Tutorials with KS4 students at Springfield School, Portsmouth on antimicrobial resistance and current research on drug development and delivery strategies. |
Year(s) Of Engagement Activity | 2022 |
Description | Dr Gareth LuTheryn delivered KS3 tutorials on AMR |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Dr Gareth LuTheryn delivered a series of tutorials on antimicrobial resistance to KS3 students at Bourne End Academy, Slough and The WREN School, Reading. Over the course of 5 Weeks, 20 hours of instruction were delivered and 28 students and their families were reached. |
Year(s) Of Engagement Activity | 2023 |
Description | Dr Gareth LuTheryn presented work on antimicrobial resistance at EuroBiofilms22, Mallorca. |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Dr Gareth LuTheryn presented work on antimicrobial applications of nitric oxide microbubbles to EuroBiofilms22, Mallorca. |
Year(s) Of Engagement Activity | 2022 |
URL | https://eurobiofilms2022.com/ |
Description | Dr Heather Nesbitt presented a poster at the International Symposium for Therapeutic Ultrasound in Toronto |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Poster presentation on "New Sensitisers for Antimicrobial Sonodynamic/Photodynamic Therapy." |
Year(s) Of Engagement Activity | 2022 |
Description | Dr Ramon Garcia-Maset presented research on AMR at EuroBioFilms2022 conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Dr Ramon Garcia-Maset delivered an oral presentation titled, "Synergistic effects of synthetic nano-engineered antimicrobial -peptide polymers and antibiotics against S. aureus and P. aeruginosa biofilms in in vitro and ex vivo models." |
Year(s) Of Engagement Activity | 2022 |
URL | https://eurobiofilms2022.com/scientific-program |
Description | Dr Sara Keller presented research at the 183rd Acoustical Society of America meeting. |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Dr Sara Keller presented research on strategies for addressing antimicrobial resistance in the presentation titled, "Spatio-temporal evaluation of anti-biofilm cavitation activity by passive acoustic mapping" at the 183rd Meeting of the Acoustical Society of America in Nashville, Tennessee, USA. |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.fusfoundation.org/posts/meeting-report-183rd-meeting-of-acoustical-society-of-america-as... |
Description | Mr Christopher Campbell presented at the 28th European symposium on Ultrasound Contrast Imaging |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Mr Christopher Campbell delivered a poster presentation at the 28th European symposium on Ultrasound Contrast Imaging. The presentation focused on the topic of optimising the formulation of perfluorocarbon nanodroplets for nitric oxide delivery to chronic wound biofilms in an effort to address antimicrobial resistance. |
Year(s) Of Engagement Activity | 2023 |
URL | https://wfumb.info/event/european-symposium-on-ultrasound-contrast-imaging-in-rotterdam/ |
Description | Mr Victor Choi presented on biofilms and ultrasound-responsive mechanical disruption of at Keystone Symposia, Banff, AB, Canada. |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Mr Victor Choi delivered a conference presentation titled, "Combatting Pathogenic Biofilms through Ultrasound-Responsive Platforms for Mechanical Disruption and Drug Delivery, Novel Approaches Against Emerging Antimicrobial Resistance" at Keystone Symposia, Banff, AB, Canada in December of 2022. This was delivered as part of a chaired session with the title, "Challenges and Novel Pathways to Develop Alternative Therapies". |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.keystonesymposia.org/ |
Description | Prof. Eleanor Stride appointed to Engineering Policy Committee (Royal Academy of Engineering) |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Policymakers/politicians |
Results and Impact | Prof. Eleanor Stride appointed to Engineering Policy Committee (Royal Academy of Engineering), which led to the development of educational resources for use in primary and secondary schools, as well as information provided to policy makers on the urgency of antimicrobial resistance. |
Year(s) Of Engagement Activity | 2021 |
Description | Prof. Eleanor Stride collaborated with the Royal Academy of Engineering |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | Prof. Eleanor Stride collaborated with the Royal Academy of Engineering education team to compile educational resource packet on water pollution and antimicrobial resistance for use in schools. The educational resource is designed to provide practical and contextualised applications where students and teachers can see the role that STEM-based learning plays in real-world engineering scenarios. |
Year(s) Of Engagement Activity | 2022 |
URL | https://stemresources.raeng.org.uk/resources/enrich/this-is-engineering-water/ |
Description | Prof. Eleanor Stride contributed to workshop series on "Bubble Activity in Therapeutic Ultrasound" delivered by the Focused Ultrasound Foundation |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | The Focused Ultrasound Foundation and the American Institute of Ultrasound in Medicine's Future Fund hosted a virtual workshop series on Detecting, Mapping, and Quantifying Bubble Activity in Therapeutic Ultrasound. The objectives of the workshop were to identify the levels of knowledge, gaps in knowledge, and best practices in bubble activity dosimetry for ultrasound therapy. |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.fusfoundation.org/posts/bubble-activity-in-therapeutic-ultrasound-workshop-series/ |
Description | Prof. Eleanor Stride joined editorial board of Journal of Antibiotics in Clinical Settings |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Prof. Stride joined the Associate Editor Board of Antibiotics in Clinical Settings, which is a specialty section of the Journal, titled "Frontiers in Antibiotics". Associate Editors make an important contribution to the quality and strategic development of the section. |
Year(s) Of Engagement Activity | 2022 |
Description | Prof. Stride served as panel member on BBC Radio 4 show "Best Medicine" |
Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Prof. Eleanor Stride served as panel member on BBC Radio 4 show "Best Medicine" released on 07/07/2022. The programme informed the public about research using nano-bubbles to address AMR and for cancer therapy. |
Year(s) Of Engagement Activity | 2022 |