AFM salmonella. Credit: IFR
Salmonella enterica serovar Typhimurium (S. Typhimurium) is the most common cause of food poisoning in the EU, and worldwide S. Typhi and S. Paratyphi are responsible for 800,000 deaths each year due to contaminated food and water. Whilst efforts to prevent contamination continue, there is a clear need to develop new treatments to combat infection with Salmonella following ingestion, and to do this more knowledge of how it survives and replicates within the host is needed.
Once inside our bodies, Salmonella invades the epithelial cells that line the gut and reproduces and can become systemic by invading and growing in macrophage cells, which are part of the body’s immune defences. This shows how well Salmonella is adapted to grow in different environments, and previous work at IFR (see: www.ifr.ac.uk/info/news-and-events/NewsReleases/090519salmonellanutrition.html) has already shown that it uses different strategies to feed in different host environments.
“We inferred that Salmonella uses different pathways to generate the energy required for growth and survival in macrophages and epithelial cells,” said Dr Arthur Thompson of the Institute of Food Research. “What we want to do now is work out what these pathways are. Does Salmonella use anything from the host cells to contribute to its growth?”
The researchers have been awarded over £400,000 by BBSRC to identify the different ways in which Salmonella obtains its energy for growth and survival within the two types of host cells. They will also use cutting edge techniques to determine exactly what it is that Salmonella gets from its host cells to permit growth.
“If we can identify what Salmonella depends on for growth in the cells, we may be able to design new therapeutic agents to block this happening and prevent its growth.”
About the project: Importance of the intracellular energy metabolism of S. Typhimurium within epithelial cells and macrophages
This is collaborative project with Prof. Dave Kelly at the University of Sheffield and Dr. Fran Mulholland at the IFR, and is based on previous externally funded BBSRC research carried out at the IFR, and awarded to Dr. Thompson. According to the latest European Food Standard Agency (EFSA) statistics (2008), Salmonella enterica serovar Typhimurium (S. Typhimurium) is the second most reported zoonotic infection in humans and the most frequent cause of food borne outbreaks in the EU. Worldwide Salmonella is responsible for up to 800,000 deaths from contaminated food and water. As part of its infection cycle, Salmonella invades and replicates with the epithelial cells lining the gut followed by invasion and growth within macrophages. One of the major questions in infection biology is how the metabolism of Salmonella changes and adapts to enable growth and survival within host cells. Our previous work showed, for the first time, that glucose and glycolysis are essential for Salmonella to survive and grow within macrophages, but not within epithelial cells. Based on this discovery, and other data, we surmised that Salmonella uses different pathways to generate the energy required for growth and survival in macrophages and epithelial cells. The new project will tell which energy generating pathways uses in these two types of host cells, which will have major consequences for the virulence of Salmonella. A further important question in infection biology is the extent to which the host cell contributes to the intracellular growth of Salmonella. We will use cutting edge techniques to determine the contribution of amino acids derived from host proteins and peptides to the intracellular growth of Salmonella in infected epithelial cells and macrophages. If Salmonella is dependent on the host for some of its requirements to enable intracellular growth, then this may also represent a way to facilitate therapeutic intervention.
BBSRC invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond.
Funded by Government, and with an annual budget of around £445M, we support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals.
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