The evolutionary emergence of multidrug resistant bacterial pathogens
Lead Research Organisation:
University of Manchester
Department Name: School of Biological Sciences
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Planned Impact
Who will benefit and how?
This is fundamental blue-skies research but results from this programme of research, and its practical application in clinical and environmental management of antibiotic use, has the potential to deliver far-reaching benefits across a wide range of sectors, from individuals and organizations, to societal benefits from long-term potential gains in the overall lifespan of existing and new antibiotics. The mechanistic understanding of the evolution of antibiotic resistance gained from this project will enable informed clinical decisions of antibiotic use, potential biomarkers of high-risk emerging pathogenic strains, and improved advice to the veterinary and farming community on the use of antibiotics. Although banned now in the EU, use of antibiotics as growth promoters is still widespread elsewhere - up to 40% of antibiotics used are as livestock growth promoters. The beneficiaries of this project can be divided in to 2 groups:
1) General Public: AMR is high on the news agenda, with recent reports of colistin resistance bacteria in China widely reported in the UK and beyond. Despite this, in August 2015, a report from NICE (National Institute for Health and Care Excellence) claimed that 10 million doses of antibiotics are inappropriately prescribed in the UK each year. We envisage that one key strand of impact activities associated with our project will be directed towards improving public understanding of the impending societal crisis surrounding rising antimicrobial resistance. There exists widespread misunderstanding of antimicrobial resistance (AMR) among the general public as shown by recent Wellcome Trust research ("Exploring the consumer perspective on antimicrobial resistance" report). The report identifies 3 key challenges:
1. Public attitudes to antibiotics and treatment are a barrier to improving antibiotic stewardship.
2. Poor knowledge of how antibiotics work and what resistance means lead to misconceptions about the nature of the AMR problem.
3. "Doomsday" scenarios and the huge numbers surrounding the AMR crisis in the media make individuals feel powerless to effect change.
Public engagement events designed to reach different age groups in schools and the wider community will raise awareness of the science underpinning the evolution of antibiotic resistance, and what we can all do to minimise the risk. We will leverage the high-profile of Antibiotic Action, based at UoB, to promote the events and key findings among the general public.
2) Government, Clinical, Agriculture and Veterinary Policymakers: AMR is also high on the policy agenda, with antibiotics of last resort increasingly at risk. Many reports across all these areas are highlighting AMR as a concern, yet there is a dearth of knowledge about the evolutionary mechanisms of AMR emergence particularly in pathogens affecting both humans and animals and where AMR arises through horizontal gene transfer. Our findings will be communicated to key stakeholders that can impact the use of antibiotics and their dissemination in clinical and agri-food environments, including: medical professionals, veterinarians, farmers and the agri-food industry.
This is fundamental blue-skies research but results from this programme of research, and its practical application in clinical and environmental management of antibiotic use, has the potential to deliver far-reaching benefits across a wide range of sectors, from individuals and organizations, to societal benefits from long-term potential gains in the overall lifespan of existing and new antibiotics. The mechanistic understanding of the evolution of antibiotic resistance gained from this project will enable informed clinical decisions of antibiotic use, potential biomarkers of high-risk emerging pathogenic strains, and improved advice to the veterinary and farming community on the use of antibiotics. Although banned now in the EU, use of antibiotics as growth promoters is still widespread elsewhere - up to 40% of antibiotics used are as livestock growth promoters. The beneficiaries of this project can be divided in to 2 groups:
1) General Public: AMR is high on the news agenda, with recent reports of colistin resistance bacteria in China widely reported in the UK and beyond. Despite this, in August 2015, a report from NICE (National Institute for Health and Care Excellence) claimed that 10 million doses of antibiotics are inappropriately prescribed in the UK each year. We envisage that one key strand of impact activities associated with our project will be directed towards improving public understanding of the impending societal crisis surrounding rising antimicrobial resistance. There exists widespread misunderstanding of antimicrobial resistance (AMR) among the general public as shown by recent Wellcome Trust research ("Exploring the consumer perspective on antimicrobial resistance" report). The report identifies 3 key challenges:
1. Public attitudes to antibiotics and treatment are a barrier to improving antibiotic stewardship.
2. Poor knowledge of how antibiotics work and what resistance means lead to misconceptions about the nature of the AMR problem.
3. "Doomsday" scenarios and the huge numbers surrounding the AMR crisis in the media make individuals feel powerless to effect change.
Public engagement events designed to reach different age groups in schools and the wider community will raise awareness of the science underpinning the evolution of antibiotic resistance, and what we can all do to minimise the risk. We will leverage the high-profile of Antibiotic Action, based at UoB, to promote the events and key findings among the general public.
2) Government, Clinical, Agriculture and Veterinary Policymakers: AMR is also high on the policy agenda, with antibiotics of last resort increasingly at risk. Many reports across all these areas are highlighting AMR as a concern, yet there is a dearth of knowledge about the evolutionary mechanisms of AMR emergence particularly in pathogens affecting both humans and animals and where AMR arises through horizontal gene transfer. Our findings will be communicated to key stakeholders that can impact the use of antibiotics and their dissemination in clinical and agri-food environments, including: medical professionals, veterinarians, farmers and the agri-food industry.
Organisations
People |
ORCID iD |
Michael Brockhurst (Principal Investigator) |
Publications
Billane K
(2022)
Why do plasmids manipulate the expression of bacterial phenotypes?
in Philosophical transactions of the Royal Society of London. Series B, Biological sciences
Brockhurst MA
(2022)
Ecological and evolutionary solutions to the plasmid paradox.
in Trends in microbiology
Carrilero L
(2021)
Positive Selection Inhibits Plasmid Coexistence in Bacterial Genomes
in mBio
Hall R
(2024)
Multidrug resistance plasmids commonly reprogram the expression of metabolic genes in Escherichia coli
in mSystems
Kottara A
(2021)
The dilution effect limits plasmid horizontal transmission in multispecies bacterial communities.
in Microbiology (Reading, England)
Description | Bacteria can become resistant to antibiotics by acquiring copies of resistance genes from other cells, however these resistance mechanisms are frequently costly to express in the new cell. We show that evolution can rapidly produce bacteria that are highly resistant to antibiotics but no longer have to pay the cost. Published in ISME Journal. We have published a major review on the role of mobile genetic elements in the evolution of bacterial genomes. Published in Current Biology. We have published an opinion article on ways to improve assessments of the risk of resistance evolution to new antibiotics. Published in Nature Ecology and Evolution. We published a review paper about the various mechanisms that enable the maintenance of plasmids in bacterial genomes. Published in Trends in Microbiology. Using lab experiments we have shown that plasmids alter how bacterial genes are regulated in a strain-specific manner (published in mSystems). Using lab experiments we have shown that multiple plasmids cannot coexist in the same bacterial genome if they encode the same beneficial function (published in mBio). We used lab experiments and genome sequencing to test how diverse bacteria adapt to acquiring a multidrug resistance plasmid. We show that diverse bacteria follow some common evolutionary pathways to gain mutations that fix alterations in key cellular processes, such as metabolism, caused by the plasmid. Published in mSystems. |
Exploitation Route | These findings help to explain how multidrug resistance plasmids are maintained and spread in bacterial populations, which is relevant to understanding the spread of antibiotic resistance. |
Sectors | Agriculture Food and Drink Healthcare Pharmaceuticals and Medical Biotechnology |
URL | https://www.biorxiv.org/content/10.1101/2020.10.23.351718v1 |
Description | Team members have spoken at a range of public engagement events reaching around 800 people including school children and members of the general public, including raising awareness of drug resistant infections with high-risk groups. These talks have sparked questions from the audience and led to increased interest in the subject area. We published a comic book based on the research in this project written by Edward Ross "Luna and Simon: Bizarre Bacteria and Peculiar Plasmids". Printed and Online. https://www.andthemicrobes.org |
First Year Of Impact | 2018 |
Sector | Agriculture, Food and Drink,Creative Economy,Digital/Communication/Information Technologies (including Software),Education,Healthcare,Culture, Heritage, Museums and Collections |
Impact Types | Cultural Societal |
Description | Public engagement comic book |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Comic book "Luna and Simon: Bizarre Bacteria and Peculiar Plasmids" written by Edward Ross based on our research and accompanying website. Printed and online. Production featured workshops for 20 school children. Over 500 printed copies have been distributed and far more downloaded from the website. |
Year(s) Of Engagement Activity | 2020 |
URL | https://www.andthemicrobes.org |
Description | School Visit |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Talk and discussion with ~50 pupils at Bramhall High School in Stockport about phages and phage therapy using the andthemicrobes.org comics as lesson tools |
Year(s) Of Engagement Activity | 2023 |
URL | https://www.andthemicrobes.org |