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;在孟加拉国、南美地区、非洲和澳大利亚以及美国墨西哥湾沿岸流行，在所有水生环境中都有可能流行。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本地水生植物群成员的地区引起周期性、季节性爆发，这种能力与其在不同环境条件下的生存有关。霍乱弧菌在环境胁迫下，其菌落形态从光滑半透明型转变为褶皱不透明型，称为皱纹变体。我们推测，相变化介导的种群组成的变化，霍乱弧菌可以增加水生生存的机会。该项目的长期目标是了解霍乱弧菌如何在流行病之间生存，重点是光滑到皱纹阶段变化的分子机制，其生理后果及其对生物体水生生存的影响。 为实现这一目标，我们将重点实现以下具体目标：1）确定和表征光滑到皱纹相变化的分子基础，2）表征控制皱纹特异性基因表达的转录网络，并表征生物体中由相位变化引起的生理和行为变化3）阐明不同的环境参数对平滑和皱纹变体的水生生存特性和相位变化频率的影响。 了解平滑到皱纹的阶段变化如何有助于环境水生栖息地中霍乱弧菌O 1 El Tor的持久性和生存，以及阐明调节阶段变化的基因和过程将进一步加深我们对重要人类病原体的水生生命周期的理解。从这项研究中获得的结果应导致分子工具，可用于识别转录本或蛋白质，预测提供更好的环境适应性的生物体在自然水生栖息地的发展。这一信息将证明有助于预测和/或控制霍乱流行。平滑到皱纹的阶段变化在公共卫生中提出了另一个挑战，因为这个过程使生物体对氧化应激和氯介导的杀伤具有抗性。氯化被用作抵御霍乱弧菌和许多其他水媒病原体的第一道防线。了解相位变化的机制和调节可能有助于设计用于调节相位变化频率的方法/抑制剂，从而调节霍乱弧菌和其他水生病原体中的杀生物剂抗性。

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.