How is V. cholerae lifestyle switching controlled?

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Vibrio cholerae is a bacterium. It is the biological agent that causes Cholera, a severe form of diarrhoea. Worldwide, approximately 4 million people are infected by V. cholerae every year. This results in hundreds of thousands of fatalities. Many cases are attributable to an ongoing global pandemic, the 7th to sweep our planet in recorded history. However, disease is also associated with local epidemics; the upsurge of Cholera cases in Haiti, following the 2010 earthquake, being of note. The annual financial cost associated with V. cholerae infections exceeds $3 billion annually. Hence, there is significant commercial interest in solving the "Cholera problem". At present, epidemics may be controlled by vaccinating the population in affected areas. However, currently available Cholera vaccines are poorly effective. Consequently, industrial operations worldwide are identifying strategies to develop better vaccines. The growing problem of resistance to antimicrobial agents is also fueling this trend. The ability of V. cholerae to persist in the environment, and cause disease, is dependent on exploitation of two different environmental niches. Principally, V. cholerae is an aquatic organism that colonises the surface of crustaceans. In this situation, the bacterium's primary source of nutrition is chitin; a component of the shellfish exoskeleton. Thus, V. cholerae forms biofilms on such surfaces. Conversely, when V. cholerae is ingested by fish, or humans, the bacterium's lifestyle is "reprogrammed" so that it can colonise the host. This is beneficial to the bacterium since it can multiply rapidly in hosts before being shed back into the environment. In humans this process is associated with the disease known as Cholera. Understanding how V. cholerae adapts to its different environments is therefore of great interest.In recent work we have shown how applying the next generation of experimental tools can rapidly progress our understanding of bacterial pathogens. We propose to apply such tools to understand lifestyle switching in V. cholerae. Ultimately, by picking apart the control of lifestyle switching, and redesigning V. cholerae to regulate this process differently, we hope to stimulate a new era of vaccine design. We expect that this approach will be applicable to many diseases caused by bacteria. We have identified UK based biopharma likely to benefit from these advances and will liaise closely with them throughout the project. The purpose of this interaction is to maximise the impact of our work and to exploit opportunities that arise for commercialisation. In summary, we will study a globally important pathogen and develop strategies applicable to the control of all bacteria. Importantly, this application comes at a time when alternatives to antibiotics are being sought and the window of opportunity to act is open. We have already fostered links with important "end-users" of our data to maximise the economic impact of our work.