s-RNA-based therapeutics for disease caused by A. pleuroneumoniae

Abstract
The bacterium Actinobacillus pleuropneumoniae (APP) causes is a highly contagious lung disease in pigs which affects herds in the UK and worldwide. Infection results in either rapid mortality or slow growth, breathing problems and suffering. APP is responsible for substantial economic losses to the worldwide pig industry.

After good husbandry practices (provision of good ventilation, all in/all out facilities, avoidance of temperature fluctuations and good hygiene) are taken into account there are two basic methods used to limit APP infection: namely vaccines and antibiotics. However, current vaccines have severe limitations and antibiotic resistance is of increasing concern, a recent survey suggesting that 70% of APP isolates in the UK are now resistant to one or more antibiotics. Consequently, there is an urgent need for effective therapeutic approaches to combat APP. Addressing such issues directly aligns to the key BBSRC strategic priorities of 'Animal Health', 'Welfare of Managed Animals' and 'Combating Antimicrobial Resistance'.

Traditional antibiotics seek to simply kill bacteria, but a novel therapeutic alternative is to target functions that are essential for the bacteria's ability to infect the host. Such an approach effectively disarms the bacteria, rather than killing them, thereby avoiding the selective pressure from which traditional antibiotic resistance originates. Bacterial cells, such as APP, have important switching molecules (sRNAs) which are responsible for turning on the mechanisms that enable host infection to occur. Our proposal plans to identify these crucial sRNAs in APP and then inhibit their function using compounds called peptide nucleic acids (PNAs). Targeting the sRNAs in this manner will lead to a new therapeutic approach for treating APP disease. More broadly, this research also provides the basis for exploring sRNA inhibition as an alternative therapeutic approach to bacterial diseases caused by other major pathogens of animals and man.

This work is innovative, timely and multi-disciplinary, building on recent work and employing the latest molecular tools and technological advances to deliver results. This is a joint collaborative venture which benefits from the synergy between world leading expertise in APP (Imperial College London) and an outstanding track record in sRNA research (University of Portsmouth). Within this context, the project has a substantial chance of success, standing to offer a step change in capability for treating APP, but with far reaching impact for the therapeutic treatment of bacterial diseases more broadly.