Smooth to Rugose phase variation in Vibrio cholerae

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海湾地区都有霍乱。 在所有水生环境中都有可能流行的美国海岸。据估计，有12万人 全世界每年都有人死于霍乱。霍乱弧菌在其所在地区引起周期性、季节性暴发 土著水生植物群的现有成员，这一能力与其在多样化环境下的生存有关 环境条件。霍乱弧菌的菌落形态从光滑和半透明变为皱纹 以及暴露在环境压力下的不透明类型，称为皱纹变种。我们假设这一阶段 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存活机会 有机体。这个项目的长期目标是了解霍乱弧菌是如何在霍乱流行期间生存的 光滑相向皱纹相转变的分子机制、生理后果及其对细胞周期的影响 在水中生存的有机体。 为了实现这一目标，我们将着重于以下具体目标：1)确定和表征分子基础 平滑到皱纹的阶段变化，2)表征了控制皱纹糖特异基因的转录网络 表达和表征由相变引起的生物体的生理和行为变化3) 不同环境参数对锯齿鱼水生生存特性的影响 变种和相位变化的频率。 了解光滑到具皱纹的阶段变化如何有助于沙门氏菌O1的持久性和存活率 环境水生生境中的El Tor，以及调节阶段变化的基因和过程的阐明将 进一步加深了我们对水生生物生命周期中一种重要的人类病原体的认识。这项研究的结果 应该会导致分子工具的发展，这些工具可以用来识别预测的转录本或蛋白质 为自然水生生境中的生物体提供更好的环境适应性。这些信息将被证明在 霍乱疫情的预测和/或控制。平滑到皱纹的相位变化带来了另一个挑战 因为这一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。 了解相变的机制和调节有助于设计用于调制的方法/抑制剂 霍乱弧菌和其他水生病原体的相变频率和抗药性。

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 epidemic 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 tong 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. choterae O1 El Tor in environmental aquatic habitats, and elucidation of the genes and processes regulating the phase variation will further our understanding of 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.