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  Project at Brunel University: Repurposing artificial sweeteners as infection and contamination control agents.


   FoodBioSystems DTP

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  Dr R McCarthy, Prof Brendan Gilmore  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

This project would be suitable for students with a strong interest in antibiotic resistance and biofilms with a BSc honours degree at upper second-class level (or equivalent) in Microbiology/Biomedical Sciences or a closely related subject.

Project outline

Artificial sweeteners are a group of compounds that have a significantly higher sweetening power than sucrose but have little to no calorific contribution. Because of these properties, artificial sweeteners have become mainstays in the human diet with many companies offering “Zero” or “Sugar Free” alternatives to typically high sugar products. While there have been extensive studies investigating the impact of these sweeteners on the human body (Carocho et al., 2017), there have been relatively few studies looking at the impact of these compounds on the bacteria in the human body. However, there is emerging evidence that artificial sweeteners can significantly alter the gut and oral microbiome and that these changes can have an impact on human health (Suez et al., 2022). A recent study by the McCarthy lab has demonstrated that a number of these artificial sweeteners possess antimicrobial properties with the highly popular sweetener acesulfame-K (ace-K) in particular, being able to inhibit bacterial movement, their ability to acquire antibiotic resistance genes from the environment and their ability to grow. In this project we want to repurpose this sweetener as an infection and contamination control agent.

Bacterial infection is a major challenge to the agrifood sector with wound infections such as digital dermatitis (a wound infection of the hoof which leads to lameness) having a major impact of livestock welfare and presenting a significant economic challenge (Palmer & O’Connell., 2015). Digital dermatitis is highly prevalent particularly in dairy farms with 70-95% of herds showing signs of digital dermatitis. The treatment of such wound infections in livestock presents a number of challenges such as the restricted contact time between the site of infection and the treatment, and the formation of bacterial communities called biofilms within the wounds. Biofilms are communities of bacteria encased in polysaccharide matrix, by growing in biofilms, bacteria are between 10-1,000 more resistant to antibiotic therapy and chemical disinfection (Maslova et al., 2021). The increasing restrictions on the use of antibiotics in agriculture also complicates the treatment landscape (Manyi- Loh et al., 2018). 

Bacterial contamination in food processing is a major cause of foodborne illness, food spoilage and production pipeline shuts downs. This contamination is particularly problematic and difficult to eradicate when bacteria adopt the biofilm mode of growth. These biofilms can form within key parts of the food processing infrastructure leading to costly plant shuts downs and damaging decontamination procedures (Galie et al., 2018).

In this project we will explore the ability of the artificial sweetener, ace-K , to treat livestock associated wound infections and assess its ability to act a surface decontamination agent. We will address this through three distinct but interlinked objectives. 

1) Determine the ace-K spectrum of antimicrobial activity (BUL): In this objective we will investigate which foodborne pathogens are susceptible to the antimicrobial activity of ace-K and at what concentrations. We will also explore the basic physiological consequences of ace-K exposure to these pathogens using live cell imaging. To determine if ace-K can influence the transmission of antibiotic resistance genes within livestock, we will use simulated porcine gut microbiota model and an ex vivo skin microbiota model to study horizontal gene transfer. 

2) Investigate the ability of artificial sweeteners to treat wound infections in livestock (BUL &QUB): Ace-K has been shown to be effective at preventing biofilm formation and disrupting established biofilms. This proposal will explore its ability to treat and prevent wound infections in livestock using ace-K wash solutions and ace-K loaded hydrogel wound dressings in an ex vivo porcine wound model.

3) Determine the capacity of artificial sweeteners to decontaminate contaminate surfaces (BUL &QUB): We will use 3D printed replica models of food processing pipelines and surfaces to assess the ability of ace-K loaded wash solutions to prevent surface contamination. 

Ace-K is a compound consumed by millions of people on a daily basis and its ability to prevent pathogen growth has only recently been recognised. This project will build on this finding by generating new insights into the fundamental biology of how ace-K kills foodborne pathogens and assessing its capacity be used as an infection and contamination control agent. Repurposing this food additive as a biocontrol agent could offer viable therapeutic and decontamination solutions to a variety of stakeholders in the agrifood sector.

Training

The prospective student will gain experience and training in a wide range of molecular biology and microbiological methods. This will include live cell imaging and within host horizontal gene transfer assays. They will also gene experience in pharmaceutical formulation and wound therapy development as well as in ex vivo porcine wound assays to determine treatment efficacy. The student will also gain experience in computer aided design, 3D printing and in the use of flow cell biofilm assays. The student will also play a central role in communicating project goals and progress with stakeholders.

How to Apply

Applications will be by online application form only. Do not send CVs. Please go to the FoodBioSystems website to see guidance for applicants, information on academic and funding eligibility and language proficiency.

Equality Diversity and Inclusion:

The FoodBioSystems DTP is committed to equality, diversity and inclusion. We want to build a doctoral researcher and staff body that reflects the diversity of society, and to encourage applications from under-represented and disadvantaged groups. Our actions to promote diversity and inclusion are detailed on the FoodBioSystemsDTP website.


Agriculture (1) Biological Sciences (4) Engineering (12) Food Sciences (15) Veterinary Sciences (35)

Funding Notes

FoodBioSystems DTP students receive a tax free stipend (salary) for four years. For 2023/24 this is £18,622 (or £20,622 for students based at Brunel University). The pay increases slightly each year at rate set by UKRI. The DTP also pays tuition fees at the standard UK rate and makes a contribution to the research project costs.
Most of our funding (minimum 70%) is available to students with UK/home fees status. We welcome applications from international students. However, we can only offer up to 30% of our studentships to international students. In 2024, this will be maximum of 9 projects.

References

• Carocho M, Morales P, Ferreira ICFR. Sweeteners as food additives in the XXI century: A review of what is known, and what is to come. Food Chem Toxicol. 2017 Sep;107(Pt A):302-317. doi: 10.1016/j.fct.2017.06.046. Epub 2017 Jul 5. PMID: 28689062.
• de Dios R, Proctor CR, Maslova E, Dzalbe S, Rudolph CJ, McCarthy RR. Artificial sweeteners inhibit multidrug-resistant pathogen growth and potentiate antibiotic activity. EMBO Mol Med. 2022 Nov 22:e16397. doi: 10.15252/emmm.202216397. Epub ahead of print. PMID: 36412260.
• Galié S, García-Gutiérrez C, Miguélez EM, Villar CJ, Lombó F. Biofilms in the Food Industry: Health Aspects and Control Methods. Front Microbiol. 2018 May 7;9:898. doi: 10.3389/fmicb.2018.00898. PMID: 29867809; PMCID: PMC5949339.
• Manyi-Loh C, Mamphweli S, Meyer E, Okoh A. Antibiotic Use in Agriculture and Its Consequential Resistance in Environmental Sources: Potential Public Health Implications. Molecules. 2018 Mar 30;23(4):795. doi: 10.3390/molecules23040795. PMID: 29601469; PMCID: PMC6017557.
• Maslova E, Eisaiankhongi L, Sjöberg F, McCarthy RR. Burns and biofilms: priority pathogens and in vivo models. NPJ Biofilms Microbiomes. 2021 Sep 9;7(1):73. doi: 10.1038/s41522-021-00243-2. PMID: 34504100; PMCID: PMC8429633.
• Palmer MA, O'Connell NE. Digital Dermatitis in Dairy Cows: A Review of Risk Factors and Potential Sources of Between-Animal Variation in Susceptibility. Animals (Basel). 2015 Jul 13;5(3):512-35. doi: 10.3390/ani5030369. PMID: 26479371; PMCID: PMC4598691.
• Suez J, Cohen Y, Valdés-Mas R, Mor U, Dori-Bachash M, Federici S, Zmora N, Leshem A, Heinemann M, Linevsky R, Zur M, Ben-Zeev Brik R, Bukimer A, Eliyahu-Miller S, Metz A, Fischbein R, Sharov O, Malitsky S, Itkin M, Stettner N, Harmelin A, Shapiro H, Stein-Thoeringer CK, Segal E, Elinav E. Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. Cell. 2022 Sep 1;185(18):3307-3328.e19. doi: 10.1016/j.cell.2022.07.016. Epub 2022 Aug 19. PMID: 35987213.

Where will I study?

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