How is V. cholerae lifestyle switching controlled?

霍乱弧菌是一种细菌。它是导致霍乱的生物制剂，霍乱是一种严重的腹泻。全世界每年约有400万人感染霍乱弧菌。这导致了数十万人死亡。许多病例可归因于一场持续的全球大流行，这是有记录以来第七次席卷我们这个星球的大流行。然而，疾病也与地方流行病有关；值得注意的是，2010年地震后海地霍乱病例激增。每年与霍乱弧菌感染相关的财务成本超过30亿美元。因此，解决“霍乱问题”具有重大的商业利益。目前，疫情可以通过为受影响地区的人口接种疫苗来控制。然而，目前可用的霍乱疫苗效果不佳。因此，世界各地的工业企业都在确定开发更好疫苗的战略。日益严重的抗菌剂耐药性问题也助长了这一趋势。霍乱弧菌在环境中生存并致病的能力取决于对两个不同环境生态位的开发。霍乱弧菌主要是一种栖息在甲壳类表面的水生生物。在这种情况下，细菌的主要营养来源是甲壳素；甲壳素是贝类外骨骼的一种成分。因此，霍乱弧菌在这样的表面上形成了生物膜。相反，当霍乱弧菌被鱼或人类摄入时，细菌的生活方式会被重新编程，从而能够在宿主上定居。这对细菌是有利的，因为它可以在宿主中快速繁殖，然后再排放回环境中。在人类中，这一过程与称为霍乱的疾病有关。因此，了解霍乱弧菌如何适应不同的环境是非常有意义的。在最近的工作中，我们展示了应用下一代实验工具如何快速提高我们对细菌病原体的理解。我们建议应用这些工具来了解霍乱弧菌的生活方式转变。最终，通过打破对生活方式转变的控制，并重新设计霍乱弧菌来以不同的方式调节这一过程，我们希望刺激疫苗设计的新纪元。我们预计，这种方法将适用于许多由细菌引起的疾病。我们已经确定了总部设在英国的生物制药公司可能从这些进展中受益，并将在整个项目期间与他们密切联系。这种互动的目的是最大限度地发挥我们工作的影响，并利用出现的商业化机会。总之，我们将研究一种全球重要的病原体，并制定适用于控制所有细菌的策略。重要的是，这一申请是在人们正在寻找抗生素的替代品并且采取行动的机会之窗敞开的时候提出的。我们已经与我们数据的重要“最终用户”建立了联系，以最大限度地发挥我们工作的经济影响。

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.