Battling biofilms: developing better ways to eradicate bacterial contamination (WEBBER_Q17ICASE)

Lead Research Organisation: University of East Anglia
Department Name: Graduate Office

Abstract

Bacterial infection remains a major cause of morbidity and mortality and our ability to treat infection is being challenged by the development of antibiotic resistance, prevention of infection is more important than ever. Most bacterial infections of humans and animals and contamination of food products and industrial processes involves bacteria in a biofilm. Biofilms are aggregates of bacterial cells in a complex community and bacteria in a biofilm are inherently highly resistant to antibiotics and other antimicrobials including some disinfectants. Recently we have documented how bacteria respond to disinfectant stress and shown that some disinfectants can select for antibiotic resistant mutants in planktonic culture. We now aim to investigate the impact of biofilm formation on these processes.

Cleaning and disinfection are the main current routes used to try and eradicate biofilms from critical surfaces although this is often unsuccessful which can lead to outbreaks of infection or contamination. This project is offered in conjunction with the research and development team of Procter & Gamble UK (P&G) and aims to:

Understand how bacteria respond to disinfection challenge and what impact this has on antibiotic resistance
Develop improved models to test disinfectant activity against biofilms
Compare the efficacy of different disinfectants in killing biofilms to help develop improved products

The project will combine a mixture of microbiology, genetics and microscopy approaches to understand bacterial stress responses and the ability of different disinfectants to kill or promote evolution of pathogenic bacteria.

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011216/1 01/10/2015 30/09/2023
1941124 Studentship BB/M011216/1 01/10/2017 30/09/2021 Gregory Wickham
 
Description This work has thus far developed and validated a model system for studying the evolutionary dynamics of adaptation to selective pressures in biofilms. Using experimental evolution, adaptation of biofilms to selective pressures in a closed system can be modeled in the laboratory setting as demonstrated by selection for increased biofilm formation and antimicrobial resistance within experimental timeframes.

Importantly, selection for biofilm hyperproduction can occurred on all clinically- and industrially-relevant substrates tested. Characterisation of these experimentally evolved strains show that despite biofilms being traditionally considered more intrinsically resistant to antimicrobials, biofilm hyperproduction does not confer any decrease in susceptibility in a monospecies system, challenging the accepted dogma. This opens a new area to explore as biofilm-related infections are more difficult to treat which is generally attributed to increased intrinsic resistance. If this is not the case it may be that biofilm hyperproducers possess other properties which confer difficulty to eradicate enhanced including tolerance to generic stresses or resistance-independent persistence which will be investigated.

This work has also revealed a selective interface between development of biofilm formation and antimicrobial resistance, as selection for biofilm hyperproduction does not occur when exposed to increasing challenge from antimicrobials, indicating an evolutionary trade-off between the two selective pressures. This will be explored further to develop an understanding of how antimicrobial resistance and biofilm formation is co-selected. This will include whether development of resistance in constrained or compensated in biofilm hyperproducing strains and vice versa and if disparate evolutionary trajectories to resistance are selected in biofilms and planktonic cultures.

This work has also shown that adaptation to non-therapeutic antimicrobials can modulate susceptibility to clinically-relevant antibiotics. This is important as the ubiquity of antimicrobial agents in agriculture, consumer goods and industry may be important drivers of antimicrobial resistance, acting to select and maintain resistance in the absence of antibiotics. This is being investigated further and a broad range of antimicrobial agents are being examined for their cross-selective potential.
Exploitation Route This work aims to generate a cross-sectional narrative on how biofilms adapt to antimicrobial stress and how non-antibiotic antimicrobials modulate susceptibility to antibiotics. This could be taken forward by industrial partners by making evidence-based changes to biofilm decontamination regimes if it is determined that current protocols have the potential to select for antimicrobial resistant or environmentally persistent biofilms. Furthermore, this work offers a fundamental understanding into the nature of selective procceses in biofilms and offers the basis of developing techniques which could be translated into preventing biofilm colonisation from the outset.
Sectors Agriculture, Food and Drink,Environment,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Title Biofilm evolution model 
Description Development of a biofilm evolution model to study bacterial responses to stress in biofilms 
Type Of Material Technology assay or reagent 
Year Produced 2018 
Provided To Others? Yes  
Impact Collaborative research project with Procter and Gamble Submitted grant applications Hosted training events for collaborating groups to allow transfer of the technology 
 
Description Oral presentation given at the British Council-National Natural Science Foundation of China Joint Workshop on Understanding Drivers of Antimicrobial Resistance in the Food Chain 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presented during the British Council-National Natural Science Foundation of China Joint Workshop on Understanding Drivers of Antimicrobial Resistance in the Food Chain describing an experimental model to study evolutionary adaptation in biofilms to conference delegates Aimed to disseminate knowledge of how experimental evolution can be used as a tool to study selective pressures including biofilm hyperproduction and antimicrobial resistance. Also presented work on how zinc sulphate, a non-antibiotic growth promoter used in livestock can select for cross-resistance to colistin and meropenem. Engaged in discussion with several people who offered insight into further developing the work and made connections with the potential for future collaboration during the conference and have had a number of requests for further information since.
Year(s) Of Engagement Activity 2019
 
Description Poster presentation at British Society for Antimicrobial Chemotherapy Antimicrobial Resistance Mechanisms for Researchers Workshop 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presented poster describing the the effects of adaptation of biofilms to quaternary ammonium compounds on susceptibility to antibiotics to conference delegates at the BSAC ARM meeting 2018. Aimed to disseminate knowledge of how biofilms adapt differently to antimicrobials and how non-therapeutic antimicrobials can modulate susceptibility to antibiotics
Engaged in discussion with several people who offered insight into further developing the work and made connections with the potential for future collaboration.
Year(s) Of Engagement Activity 2018
 
Description Poster presentation at British Society for Antimicrobial Chemotherapy Antimicrobial Resistance Mechanisms for Researchers Workshop 2019 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presented poster describing an experimental model to study evolutionary adaptation in biofilms to conference delegates at the BSAC ARM meeting 2019. Aimed to disseminate knowledge of how experimental evolution can be used as a tool to study selective pressures including biofilm hyperproduction and antimicrobial resistance. Engaged in discussion with several people who offered insight into further developing the work and made connections with the potential for future collaboration.
Year(s) Of Engagement Activity 2019
 
Description Poster presentation at Microbiology Society Microbes in Medicine Focus Meeting 2019 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Presented poster describing an experimental model to study evolutionary adaptation in biofilms to conference delegates at the Microbiology Society Microbes in Medicine Focus Meeting 2019. Aimed to disseminate knowledge of how experimental evolution can be used as a tool to study selective pressures including biofilm hyperproduction and antimicrobial resistance. Engaged in discussion with several people who offered insight into further developing the work and made connections with the potential for future collaboration.
Year(s) Of Engagement Activity 2019
URL https://www.microbiologyresearch.org/content/journal/acmi/10.1099/acmi.mim2019.po0014
 
Description Stall ran at Norwich Science Festival 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Participated in running a stall at Norwich Science Festival 2018 which aimed to inform the public about the microbiology of hygiene in the home. This included talking to over 1000 members of the public about the antimicrobial nature of "antibacterial" products and common soap, how products marketed as "antibacterial" can induce cross-resistance to antibiotics and how biofilms are more difficult to eradicate than planktonic bacteria. Engaged in discussion with members of the public who articulated that they would consider a change in behaviour regarding the use of "antibacterial" products.
Year(s) Of Engagement Activity 2018