Study of transmissible forms of Vibrio Cholerae

 描述(申请人提供)：霍乱弧菌是一种通过水传播的病原体和霍乱病原体。它在淡水中传播并持续存在的能力建立了一个发生疫情的水库。然而，流行病和过度拥挤之间的强烈联系表明了一种更有效的粪便-口腔传播模式，这得到了表明霍乱在家庭中快速有效传播的研究的支持。了解影响传播和传播的细菌和环境因素将有助于更好地了解霍乱暴发，并有助于更好地采取公共卫生措施预防霍乱暴发。我们发现霍乱弧菌在生理状态下离开人类(S)，为传播和传播做好准备。然而，我们发现，促进霍乱弧菌传播和传播的基因在很大程度上是不同的，单个基因的表达只发生在正在脱落的细胞的一小部分中。因此，我们假设不同的亚群被分离，一个为传播做好准备，另一个为快速传播做准备。在目标1中，我们将通过物理分离这些不同的亚群进行表型和基因表达研究，并对其进行特征描述。在临床样本中，我们发现了一种与霍乱弧菌密切相关的裂解噬菌体。我们发现，这种噬菌体和霍乱弧菌之间存在着一种动态的军备竞赛，这种军备竞赛发生在人类和水环境中。在目标2中，我们将确定噬菌体捕食的动力学如何影响霍乱弧菌的传播和传播。我们发现，用纯化的霍乱弧菌外膜囊泡免疫可以产生识别LPSO抗原的抗体，这些抗体足以保护霍乱弧菌，并且通过免疫宿主的霍乱弧菌是无毒的。在目标3中，我们将研究传播的保护和阻断机制。这些研究将为了解霍乱弧菌如何同时促进传播和传播，普遍存在的裂解噬菌体如何影响这些过程，以及疫苗接种如何阻止感染和传播奠定基础。这一知识将加强对水传播病原体的了解，并有助于为制定针对此类病原体的可传播和传播形式的干预措施铺平道路。

 DESCRIPTION (provided by applicant): Vibrio cholerae is a water-borne pathogen and causative agent of cholera. Its ability to disseminate and persist in fresh water establishes a reservoir from which outbreaks occur. However, the strong link between epidemics and overcrowding suggests a more efficient mode of fecal-oral transmission, which is supported by studies showing rapid and efficient spread of cholera within households. Knowledge of the bacterial and environmental factors that influence dissemination and transmission would contribute to a better understanding of cholera outbreaks, and to better public health measures to prevent them. We showed that V. cholerae exits humans in a physiological state(s) primed for dissemination and transmission. However, we found that the V. cholerae genes that contribute to dissemination and transmission are largely distinct, and that expression of individual genes occurs in only a fraction of the cells being shed. Thus, we hypothesize that distinct subpopulations are shed, one primed for dissemination and the other for rapid transmission. In Aim 1, we will demonstrate and characterize these different subpopulations by physically separating them for phenotypic and gene expression studies. In clinical samples, we identified a lytic phage that closely associates with epidemic V. cholerae. We discovered a dynamic arms race between this phage and V. cholerae that is occurring within humans and aquatic environment. In Aim 2, we will determine how dynamics of phage predation impact dissemination and transmission of V. cholerae. We found that vaccination with purified V. cholerae outer membrane vesicles elicits antibodies recognizing LPS O-antigen, that these antibodies are sufficient for protection, and that V. cholerae passing through an immune host are rendered avirulent. In Aim 3, we will examine the mechanism of protection and blocking of transmission. These studies will establish a basis for understanding how V. cholerae simultaneously promotes dissemination and transmission, how pervasive lytic phages impact these processes, and how vaccination blocks infection and transmission. This knowledge will enhance understanding of water- borne pathogens and help pave the way to development of interventions that target the transmissible and disseminative forms of such pathogens.