Integrons & antibiotic resistance : modelling of integron evolutionary dynamics - BfH, ENWW

Lead Research Organisation: University of Oxford
Department Name: Interdisciplinary Bioscience DTP

Abstract

The integron is a genetic system heavily involved in the spread of antibiotic resistance in bacteria through its ability to acquire and express mobile genetic elements called gene cassettes. While the molecular mechanisms behind this system are well known, a lot remains to be discovered about the underlying dynamics of cassette acquisition and expression, especially when under the selection pressure applied by antibiotics. The aim of this project is to create, with the help of experimental data, a quantitative mathematical model of the integron evolutionary dynamics to better understand its role in the spread and expression of antibiotic resistance phenotypes.

BBSRC priorities areas:

This project falls into the BBSRC priority of combating microbial resistance due to the major role of the integron in the acquisition, expression and dissemination of antibiotic resistance genes among bacteria. We aim to tackle this problem through a systems approach, combining modelling and experimental data.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011224/1 30/09/2015 29/09/2023
1810153 Studentship BB/M011224/1 30/09/2015 31/12/2019 Celia Gabrielle Souque
 
Description My research project studies integrons, genetic platforms that allow bacteria to capture, express and re-order mobile antibiotic resistance gene cassettes. Cassette expression levels depends on their distance from the promoter, located at the start of the integron. Integrons have been hypothesized to allow bacteria to adapt quickly by reshuffling its cassette order in response to changing antibiotic pressure, such that integrons provide 'adaptation on demand'. This, however, has never been formally proved, and I aimed to confirm or challenge this 'adaptation on demand' hypothesis using both experimental evolution and mathematical modelling. Currently my results show that this hypothesis is flawed as integron cassette shuffling does not increase adaptability, but is instead deleterious for the bacteria. This put into question what we think are actually the benefits of the integron when it comes to antibiotic resistance.
Exploitation Route Mobile integrons are widespread in clinical isolates and closely linked to antibiotic resistance. This however does not seem to be due to their shuffling power. The reasons behind their spread remain to be discovered, but are crucial to reduce and limit integrons impact on the spread of antibiotic resistance.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description Drugs vs Bugs, an antibiotic resistance boardgame 
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 Using board games to fight AMR
The emergence and spread of antimicrobial resistance is especially strong in South East Asia, where some of the key roots of the resistance problem lie in lack of awareness among the community, leading to overuse of antibiotics and misunderstanding of how they work. To address this issue, game-based learning can be a powerful tool for raising awareness on important topics such as antibiotic resistance, especially with children.
During my internship at the Mahidol Oxford Research Unit (MORU) I developed a board game based on the mechanisms of antibiotic resistance, adapted to the Thai public, to raise awareness about the key behaviours leading to the spread of resistance. In 'Drugs vs Bugs' players take the role of a team of doctors treating patients infected by bacteria or viruses. While they compete against each other to be the best doctor, players have to be smart with how they use of antibiotics, as the bugs become more and more resistant. Through this game, players learn about antibiotic resistance, how does it arise, as well as what can they do to help preventing it.
After developing the game I organized and ran outreach sessions in schools around Bangkok, reaching more than 120 students, as well as play sessions alongside other public engagement activities from MORU and a Café Scientifique evening. The feedback from these events was very positive, with the majority of the players finding the game entertaining and educational.
Drugs vs Bugs will soon be available online as a free Print'n'Play educational resource, both in English and in Thai. We are continuing its evaluation in Thailand, with the final aim to gain the support of Thai public agencies to help its deployment in Thai schools. I will also be presenting it at a conference on AMR education and aim to publish the findings of our impact study.
Year(s) Of Engagement Activity 2018
URL https://bugsinbangkok.wordpress.com/
 
Description Outreach at History of Science Museum - Cardgame 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Activities organized around antibiotic resistance presented to school children as part of visits organized in the Museum of History of Science in Oxford. We created a cardgame to explain the mechanisms behind the apparition and spread of antibiotic resistance.
Year(s) Of Engagement Activity 2017,2018