Smooth to Rugose phase variation in Vibrio cholerae

描述（由申请人提供）：霍乱是一种全球性疾病；孟加拉国、南美洲、非洲和澳大利亚地区以及美国墨西哥湾沿岸的地方性疾病，在所有水生环境中都有流行的可能。据估计，全世界每年有12万人死于霍乱。霍乱弧菌在其已成为当地水生植物群成员的地区引起周期性季节性暴发，这种能力与其在不同环境条件下的生存能力有关。当暴露于环境压力时，霍乱弧菌将其殖民地形态从光滑和半透明型转变为皱褶和不透明型，称为皱褶变体。我们推测，霍乱弧菌的相位变化介导的种群组成变化可以增加该生物在水中的生存机会。该项目的长期目标是通过关注平滑期到皱褶期变化的分子机制，其生理后果及其对生物体水生生存的影响，了解霍乱弧菌如何在流行病之间生存。

DESCRIPTION (provided by applicant): Cholera is a global disease; endemic to Bangladesh, regions of South America, Africa and Australia, and also the Gulf Coast of the United States with the potential for epidemics in all aquatic environments. It is estimated that 120,000 people worldwide die from cholera annually. V. cholerae causes periodic, seasonal outbreaks in regions where it is an established member of the indigenous aquatic flora and this capacity is linked to its survival under diverse environmental conditions. V. cholerae switches its colonial morphology from smooth and translucent type to wrinkled and opaque type termed rugose variant when exposed to environmental stresses. We hypothesize that the phase variation mediated changes in population composition of V. cholerae can increase aquatic survival chances of the organism. The long term goal of this project is to understand how V. cholerae survives between epidemics by focusing on the molecular mechanism of smooth to rugose phase variation, its physiological consequences and its effect on the aquatic survival of the organism. Towards this goal, we will focus on the following specific aims: 1) determine and characterize the molecular basis of the smooth to rugose phase variation, 2) characterize the transcriptional network governing rugose specific gene expression and characterize the physiological and behavioral changes in the organism resulting from phase variation 3) elucidate the effects of diverse environmental parameters on the aquatic survival properties of the smooth and rugose variants and on the frequency of phase variation. Understanding how the smooth to rugose phase variation is contributing to persistence and survival of V. cholerae O1 El Tor in environmental aquatic habitats, and elucidation of the genes and processes regulating the phase variation will further our understanding of the aquatic life cycle of an important human pathogen. Results obtained from this study should lead to the development of molecular tools that can be used to identify transcripts or proteins that are predicted to provide better environmental fitness to the organism in natural aquatic habitats. This information will prove useful in the prediction and/or control of cholera epidemics. Smooth to rugose phase variation presents another challenge in public heath since this process renders the organism resistant to oxidative stress and chlorine-mediated killing. Chlorination is used as a first line of defense against V. cholerae and many other waterborne pathogens. Understanding the mechanism and regulation of phase variation may aid in designing methods/inhibitors for modulating the frequency of phase variation and thus biocide resistance in V. cholerae and other aquatic pathogens.