Study of transmissible forms of Vibrio Cholerae

 描述（由申请人提供）：霍乱弧菌是一种水媒病原体和霍乱病原体。它在淡水中传播和持续存在的能力建立了一个发生暴发的水库。然而，流行病与过度拥挤之间的密切联系表明存在一种更有效的粪-口传播模式，研究表明霍乱在家庭内迅速有效地传播，这一点得到了支持。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疫情，并有助于采取更好的公共卫生措施预防霍乱。我们发现，霍乱弧菌在人体内处于传播和传播的生理状态。然而，我们发现，导致传播和传播的霍乱弧菌基因在很大程度上是不同的，并且单个基因的表达仅发生在一小部分脱落的细胞中。因此，我们假设不同的亚群脱落，一个为传播做好准备，另一个为快速传播。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来证明和表征它们。在临床样品中，我们鉴定了与流行性霍乱弧菌密切相关的裂解性噬菌体。我们发现了这种噬菌体和霍乱弧菌之间的动态军备竞赛，这种竞赛发生在人类和水生环境中。在目标2中，我们将确定噬菌体捕食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接种疫苗可激发识别LPS O-抗原的抗体，这些抗体足以提供保护，并且霍乱弧菌通过免疫宿主时是无毒的。在目标3中，我们将研究保护和阻止传输的机制。这些研究将为理解霍乱弧菌如何同时促进传播和传播，普遍的溶菌作用如何影响这些过程以及疫苗接种如何阻断感染和传播奠定基础。这一知识将提高对水媒病原体的认识，并有助于为制定针对此类病原体的传播和扩散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.