Copper-induced microbiota shifts and its effect on pig-gut colonisation by sil and sopE encoding Salmonella
Lead Research Organisation:
University of Surrey
Department Name: Veterinary Medicine & Science
Abstract
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Technical Summary
We will test the hypothesis that copper (Cu)-induced gut microbiota changes in the pig provides a niche exploited by S. Typhimurium ST34 in a sil and sopE gene-dependent mechanism.
The effect on gut bacterial communities of supplementation of pig feed with therapeutic concentrations of Cu will be determined in 120 pigs on a working farm. Piglets will be weaned on a high protein diet supplemented with either 10ppm (nutritional) or 150ppm (therapeutic) Cu and the microbiota defined by metataxonomic analysis using shotgun metagenome sequencing. Computational analysis will be used to identify species and strains that differ in the two feed groups. The role of the sil and sopE genes in colonisation of the pig gut will be determined using an in vitro gut model and experimental infections of pigs. ST34 strains in which sil or sopE or both are deleted will be constructed and assessed for their ability to grow in the presence of in vitro microbiota cultures established from faecal samples collected from pigs on Cu nutritional or Cu therapeutic diets. The same ST34 strains will be tested by experimental infection of pigs from each diet.
Together, these experiments will reveal whether the sil and sopE genes increase colonisation of the pig gut and whether this is dependent on microbiota changes associated with a diet with therapeutic concentrations of copper. Gut microbiota whose composition is altered in response to therapeutic concentrations of copper will be isolated from faecal samples of pigs, and potential direct or indirect agonistic and antagonistic properties assessed by co-culture in vitro or with organic phase extracts of spent media.
In a follow-on study, and through an ongoing collaboration with the Baumler lab (UC Davis), we will test the hypothesis that specific microbiota isolates affect colonisation of Salmonella in the murine model of infection using precision microbiota editing methodology.
The effect on gut bacterial communities of supplementation of pig feed with therapeutic concentrations of Cu will be determined in 120 pigs on a working farm. Piglets will be weaned on a high protein diet supplemented with either 10ppm (nutritional) or 150ppm (therapeutic) Cu and the microbiota defined by metataxonomic analysis using shotgun metagenome sequencing. Computational analysis will be used to identify species and strains that differ in the two feed groups. The role of the sil and sopE genes in colonisation of the pig gut will be determined using an in vitro gut model and experimental infections of pigs. ST34 strains in which sil or sopE or both are deleted will be constructed and assessed for their ability to grow in the presence of in vitro microbiota cultures established from faecal samples collected from pigs on Cu nutritional or Cu therapeutic diets. The same ST34 strains will be tested by experimental infection of pigs from each diet.
Together, these experiments will reveal whether the sil and sopE genes increase colonisation of the pig gut and whether this is dependent on microbiota changes associated with a diet with therapeutic concentrations of copper. Gut microbiota whose composition is altered in response to therapeutic concentrations of copper will be isolated from faecal samples of pigs, and potential direct or indirect agonistic and antagonistic properties assessed by co-culture in vitro or with organic phase extracts of spent media.
In a follow-on study, and through an ongoing collaboration with the Baumler lab (UC Davis), we will test the hypothesis that specific microbiota isolates affect colonisation of Salmonella in the murine model of infection using precision microbiota editing methodology.
People |
ORCID iD |
Roberto La Ragione (Principal Investigator) |
Publications
Adams JRG
(2023)
Preventing bacterial disease in poultry in the post-antibiotic era: a case for innate immunity modulation as an alternative to antibiotic use.
in Frontiers in immunology
Nicholls H
(2023)
Foodborne antimicrobial resistance (AMR) research and surveillance in the UK: priorities identified through the Food Standards Agency's AMR programme review (2023).
in Journal of medical microbiology
Description | Collaboration with Sparsholt College |
Organisation | Sparsholt College Hampshire |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | The UoS team have worked with Sparsholt College to facilitate the in vivo pig trial. |
Collaborator Contribution | Sparsholt College have facilitated the in vivo pig trial. |
Impact | NA |
Start Year | 2019 |
Description | Quadram Institute |
Organisation | Quadram Institute Bioscience |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | The team at the UoS is working in collaboration with colleagues at the Quadram Institute to study the influence of copper on the gut microflora of the pig. The University of Surrey has facilitated the on Farm study and developed the in vitro pig gut model. |
Collaborator Contribution | The team at the Quadram have worked with the UoS to conduct the in vivo pig trial and collect all the associated samples. The analysis of the samples is currently ongoing. |
Impact | NA |
Start Year | 2020 |
Description | Antimicrobial resistance: a One Health issue |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Undergraduate students |
Results and Impact | A talk for the International Veterinary Students Association. |
Year(s) Of Engagement Activity | 2022 |
Description | Exploring the microbiomes of animals in health and disease |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | A talk for the JMM seminar series. |
Year(s) Of Engagement Activity | 2022 |
Description | Novel alternatives to antibiotics for use in the livestock industry |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | A talk for the the RANK prize. |
Year(s) Of Engagement Activity | 2022 |
Description | Novel alternatives to antibiotics for use in the poultry industry |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | A talk for the Poultry Science Symposium. |
Year(s) Of Engagement Activity | 2022 |