Smooth to Rugose phase variation in Vibrio cholerae

描述(申请人提供)：霍乱是一种全球性疾病；地方性流行于孟加拉国、南美洲、非洲和澳大利亚地区，以及美国墨西哥湾沿岸，可能在所有水环境中流行。据估计，全世界每年有12万人死于霍乱。霍乱弧菌在其是本土水生植物群的既定成员的地区引起周期性、季节性的暴发，这种能力与其在不同环境条件下的生存有关。霍乱弧菌在暴露于环境压力时，其菌落形态从光滑和半透明的类型转变为皱纹和不透明的类型，称为皱纹变体。我们推测，霍乱弧菌种群组成的变化可以增加霍乱弧菌在水生环境中的生存机会。该项目的长期目标是通过重点研究霍乱弧菌从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，了解霍乱弧菌在疫情之间如何生存。 为此，我们将集中于以下具体目标：1)确定和表征光滑到皱纹阶段变化的分子基础；2)表征调控皱纹病毒特异基因表达的转录网络；3)阐明不同环境参数对光滑和皱纹突变体的水生生存特性和阶段变化频率的影响。 了解霍乱弧菌从光滑到皱纹的阶段变化如何有助于霍乱弧菌O1 El Tor在环境水生生境中的持续和生存，并阐明调控这种阶段变化的基因和过程，将有助于我们进一步了解一种重要的人类病原体的水生生活史。这项研究的结果应该会导致分子工具的开发，这些工具可用于识别转录本或蛋白质，预计这些转录本或蛋白质将为自然水生生境中的有机体提供更好的环境适应性。这些信息将被证明对预测和/或控制霍乱流行是有用的。从平滑到皱纹的相变是公共卫生中的另一个挑战，因为这个过程使生物体对氧化应激和氯介导的杀戮具有抵抗力。氯化作用被用作对抗霍乱弧菌和许多其他水传播病原体的第一道防线。了解霍乱弧菌和其他水生病原菌的相变机制和调控机制，有助于设计方法和抑制物来调节霍乱弧菌和其他水生病原体的相变频率，从而产生抗药性。

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.