Brazil-Imperial College collaboration: small RNAs in A. pleuropneumoniae - from identification to application

Lead Research Organisation: Imperial College London
Department Name: Dept of Medicine

Abstract

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Publications

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Michael GB (2018) Antimicrobial Resistance in Pasteurellaceae of Veterinary Origin. in Microbiology spectrum

 
Description Actinobacillus pleuropneumoniae (APP) is a bacterium that causes lung disease in pigs and is responsible for substantial deaths, suffering and economic losses in the worldwide pig industry. There is a need for better vaccines, the design of which requires knowledge about the properties that APP has that are required for it to cause disease (virulence factors). In recent years it has become clear that the presence (expression) of virulence factors is controlled by molecules called small RNAs (sRNAs). This award was to allow a collaboration between Imperial College London and the University of Vicosa to find out how many sRNAs were present in APP, to identify which virulence factors they controlled the expression of, and to use that information to make new vaccines. Through computer-based work, we have identified c.80 sRNAs in APP, half of which have been verified by laboratory-based work. By comparing un-modified APP (wild-type) with mutants that do not produce the sRNAs, we have determined that some sRNAs are required for the virulence of APP. We, as yet, do not know which virulence factors those sRNAs control - that has proved challenging. The work led to the start of new collaboration with the University of Portsmouth who are experts in this area of research. Apart from the work with sRNAs of APP which was the main focus of the proposed research, we have also collaborated in a number of areas. These include the use of the wax moth as an infection model for APP, which is in use by many groups throughout the world and has led to a reduction in the use of animals in APP research, and investigating characteristics of APP strains from Brazil with those from other countries, especially the UK. In London, we are developing new diagnostics for APP and it is important they can be used throughout the world especially in countries such as Brazil, the fourth largest producer of pigs in the world.

In summary, the award has been highly successful is allowing a joint programme of work to be followed by Imperial College London and the University of Vicosa that has led to the discovery of new sRNAS in APP, and identification of some that are required for virulence. The award also led to a three-way collaboration with the University of Portsmouth, and we envisage that ultimately the results will allow the design of new vaccine strategies to prevent the substantial burden of disease in the worldwide pig industry caused by APP.
Exploitation Route The work contributed to a follow up BBSRC grant and is a starting point for other researchers to find sRNAs in other Pasteurellaceae.

Other work with Vicosa e.g. development of the wax moth APP infection model led to a NC3Rs grant at Imperial, and we have exported those methods to various labs around the world including China who are now routinely using it, leading to a reduction in mice and pigs used in animal research.
Sectors Agriculture, Food and Drink,Healthcare