Improving livestock resilience by understanding the role of the microbiome in viral infection progression and antibiotic resistance (FoodBioSystems DTP)

Collaborative project based at Brunel University, offered by the FoodBioSystems DTP.

Start date
1 October 2022
Duration
4 years
Application deadline
Funding source
FoodBioSystems DTP
Funding information

FoodBioSystems DTP studentships are predominantly open to students with established UK residency. Although international students (including EU countries) can apply, due to funding rules no more than 30% of the projects can be allocated to international students. The funding will include a tax free stipend and support for tuition fees at the standard UK rate (in 2021/2022 this is a minimum of £15,609 per year and £4500 per year respectively). There will also be a contribution towards research costs.

About

Pigs represent over 35% of agriculturally produced protein for consumption globally. Two major microbial threats to the UK porcine agri-sector are porcine reproductive and respiratory syndrome virus (PRRSV) and Classical Swine Fever Virus (CSFV). PRRSV is a porcine pathogen that causes respiratory disease in young pigs and reproductive failure and is endemic in Europe. It is estimated to cost the EU Agricultural sector 1.5 billion euros each year and is the second biggest threat to global protein production behind African swine fever. CSFV is an economically significant, multi-systemic, highly contagious viral disease of swine worldwide. The disease is exotic to the UK and thus notifiable, with the last major outbreak occurring in 2000 and resulted in 75,000 animals being culled across 16 farms.

The microbiome in humans has been well studied and has been shown to influence important physical functions such as energy metabolism and immune system development. Compared to humans relatively little is known about the role of the gut microbiota in pigs. This is despite a number of studies linking the pig microbiome to average daily weight gain, feed efficiency, feed conversion, feed intake and to its capacity to act as a reservoir for antibiotic resistance genes. However, there is some emerging evidence to suggest that the gut microbiome may have a role to play in respiratory viral disease severity.

We hypothesize that the gastrointestinal microbiota of pigs plays a role in the response to viral infection and modulation may improve resilience. We are in a unique position to explore this interplay between the gut microbiome and viral pathogenesis as we have partnered with the Animal and Plant Health Agency (APHA) who have agreed to give us access to a repository of faecal samples from past and upcoming CSFV and PRRSV animal studies.

We will explore this hypothesis through three distinct but interlinked Objectives.

1.      Determine the impact of PRRSV or CSFV infection on the gut microbiome: This objective will focus on analysing the specific changes that occur in the gut microbiome of pigs during viral infection. We will isolate genomic DNA from samples collected from prior PRRSV and CSFV animal studies conducted by the APHA and use Next Generation Sequencing (NGS) approaches and bespoke bioinformatic pipelines to characterise the microbial community fluctuations during PRRSV or CSFV infection relative to uninfected animals.

2.      Investigate the impact of specific bacterial species on viral replication and the host immune response: Certain bacterial species have been shown to inhibit viral replication either directly or by stimulating the immune system to produce antiviral effectors. In this objective, we will select bacterial species identified as being modulated from Objective 1 and determine their ability (or the ability of their metabolites) to inhibit viral replication. We will also investigate their ability to stimulate an antiviral immune response using co-culture assays .

3.      Explore if viral infection impacts the prevalence of antibiotic resistance genes (ARGS) in the porcine gut: Antibiotic resistance is one of the greatest threats to global healthcare systems. Antimicrobials are widely used for disease prevention and growth promotion in pigs. In fact, 80% of antibiotic use in the US is in agriculture. The One Health perspective has been critical in demonstrating the role antibiotic misuse in agriculture has in perpetuating the current antibiotic resistance crisis in hospitals (Manyi- Loh et al., 2018). We will further exploit APHA samples and use NGS approaches to determine if viral infection impacts the prevalence of ARGs within the gut microbiome.

Related links
FoodBioSystems DTP website
Training opportunities

The student will have an opportunity to gain high level bioinformatic skills. They will also develop extensive wet lab skills including the preparation of genomic libraries, next generation sequencing and the development of complex co-culture systems. They will also have the opportunity to be involved in animal studies at our partner in the Animal and Plant Health Agency.

Eligibility criteria

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

How to apply

Full details on how to apply at the FoodBioSystems page. Application by online form only. Do not send CVs, they will not be looked at.


Application deadline

Contact details

Dr Ronan McCarthy Email: ronan.mccarthy@brunel.ac.uk

References

Borey, M., Blanc, F., Lemonnier, G. et al. Links between fecal microbiota and the response to vaccination against influenza A virus in pigs. npj Vaccines 6, 92 (2021). https://doi.org/10.1038/s41541-021-00351-2

Constance LA, Thissen JB, Jaing CJ, et al. Gut microbiome associations with outcome following co-infection with porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) in pigs immunized with a PRRS modified live virus vaccine. Vet Microbiol. 2021 Mar;254:109018. doi: 10.1016/j.vetmic.2021.109018. Epub 2021 Feb 16. PMID: 33639341.

McCarthy RR, Everett HE, Graham SP, Steinbach F and Crooke HR (2019) Head Start Immunity: Characterizing the Early Protection of C Strain Vaccine Against Subsequent Classical Swine Fever Virus Infection. Front. Immunol. 10:1584. doi: 10.3389/fimmu.2019.01584

Yitbarek, A., Taha-Abdelaziz, K., Hodgins, D.C. et al. Gut microbiota-mediated protection against influenza virus subtype H9N2 in chickens is associated with modulation of the innate responses. Sci Rep 8, 13189 (2018). https://doi.org/10.1038/s41598-018-31613-0

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