Exploiting a novel chelant database to probe cellular metal-handling.
Lead Research Organisation:
Durham University
Department Name: Biosciences
Abstract
This project encompasses aspects of the Industrial Strategy related to 'Bioscience and Biotechnology' and 'Leading-edge Healthcare and Medicine'. P&G use chelants as antibacterials in personal hygiene and cleaning products, for which they hold substantive market shares. Specific challenges arise from: a) regulatory changes due to the environmental impact of persistent chelants, b) tighter restrictions on use of preservatives to avoid antimicrobial resistance, and c) the need to retain antimicrobial efficacy while meeting enforced changes in formulation. This project will develop a mechanistic understanding of the antimicrobial action of chelants to enhance microbial hostility of consumer products. The approach will enable a reduction in preservative and chelant levels whilst developing products compliant with Safety Regulations thus underpinning the use of novel alternatives to antimicrobials. In collaboration with P&G we have amassed an extensive database of effects of chelants on bacterial elemental composition and on bacterial proliferation. We will further our understanding of the antimicrobial mechanisms of action of chelants and reciprocally exploit these compounds to further knowledge of how bacterial cells handle metals. Pseudomonas aeruginosa has been selected as a target organism that presents eradication problems in existing formulations. The work is also of broader utility in combatting the threat of antimicrobial resistance (AMR), particularly in targeting wound
infections.
infections.
Publications
Chakraborti S
(2020)
A bacteriophage mimic of the bacterial nucleoid-associated protein Fis.
in The Biochemical journal
Cox HJ
(2021)
Bioinspired and eco-friendly high efficacy cinnamaldehyde antibacterial surfaces.
in Journal of materials chemistry. B
Paterson JR
(2022)
Insights into the Antibacterial Mechanism of Action of Chelating Agents by Selective Deprivation of Iron, Manganese, and Zinc.
in Applied and environmental microbiology
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/R506333/1 | 01/10/2017 | 30/09/2021 | |||
| 1935944 | Studentship | BB/R506333/1 | 01/10/2017 | 30/09/2021 | Joy Paterson |
| Description | This work has revealed more about the way that various Gram negative and Gram positive strains of bacteria respond to treatment with chelating agents (molecules that bind to positive metal ions), and is revealing more about the metal handling of these strains in the presence of competitors for the available metal ions in the environment. This research has given some indication of how bacterial metal acquisition systems can be interrupted to disrupt bacterial growth. Other key findings include investigating how Escherichia coli and Staphylococcus aureus may be able to develop resistance to these chelating agents after prolonged sub-lethal exposure. Other key data produced include insights into the interactions between these chelating agents when used in conjunction with each other, and also when used in combination with commonly used antibiotics. This should allow more effective bacterial killing and therefore greater preservation of commercial products. Research has been carried out into the response of various single-gene knock-outs in both E. coli and S. aureus to determine which genes might be of greatest significance in determining resistance or susceptibility to the different chelating agents in question. The latest findings include looking at how sub-lethal levels of these chelating agents affect metal concentrations of Pseudomonas aeruginosa. This information should reveal more about the mechanisms of action of these chelating agents, and should help to inform which chelants should be used in combination in order to provide more efficient bacterial killing. |
| Exploitation Route | In a non-academic context, the key findings of this project so far should help to inform decisions about how chelating agents could be used to help preserve commercial products; particularly within the cosmetics and healthcare industry. The novel agents investigated in the scope of this project could also form potential candidates to replace some commonly used preservatives which are persistent within the environment; minimising the environmental impact of our current cosmetic products. In the far future, these compounds may be used in topical treatment of infected wounds in a healthcare setting, or may be used in combination with conventional antibiotics to increase bacterial killing. Within an academic context, this research will reveal more about the metal acquisition pathways of various bacterial species, and how they compete for metal atoms within the environment. Future work should focus on whether it is possible to predict which species should be most susceptible to which chelating agents (either singularly or in combination). Particular genes of interest should be isolated to allow further investigation into the mechanisms of resistance that bacteria develop in response to these agents. |
| Sectors | Agriculture, Food and Drink,Environment,Healthcare,Manufacturing, including Industrial Biotechology |
| Description | Procter and Gamble |
| Organisation | Procter & Gamble |
| Country | United States |
| Sector | Private |
| PI Contribution | Investigations into business-relevant organisms, chelants and other agents have been carried out in consultation with P&G. |
| Collaborator Contribution | P&G have provided expertise in genome sequence analysis, and have shared intellectual input during meetings carried out on a bi-monthly basis. |
| Impact | Information has been shared between our research group and P&G which has impacted the direction in which the project has been headed. No materials have been provided by P&G, but they have shared expertise and intellectual input. The outputs of the study may well influence P&G formulations. |
| Start Year | 2017 |
| Description | Celebrate Science Festival |
| 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 | Several thousand primary school aged children (along with their parents/guardians) attended a large festival held over several days aimed at increasing their interest in all areas of science. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.dur.ac.uk/celebrate.science/ |
| Description | Undergraduate Open Days |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Several hundred students visited the department to find out more about undergraduate and postgraduate studies at Durham University. Some asked questions about my current project. |
| Year(s) Of Engagement Activity | 2018,2019 |