Viral Infection in Lactobacilli: An Animal BV Model

乳酸杆菌中的病毒感染：动物 BV 模型

• 批准号: 6602052
• 负责人: LIN TAO
• 金额: $ 23.38万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-15 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6602052
• 关键词: Lactobacillus; Macaca mulatta; bacterial virus; disease /disorder model; female; microorganism interaction; model design /development; vaginitis

This application is in response to the NIH RFA (AI-02-008) entitled "Impact of Microbial Interactions on Infectious Diseases." Specifically we will study the interaction between viruses (phages) and vaginal lactobacilli during the development of experimental bacterial vaginosis (BV) in animals. BV is the most common vaginal disorder affecting women worldwide. Because the cause is unknown, no methods are available to prevent BV. Although BV itself only has mild discomfort, such as discharge and fishy smell, BV is associated with two major health risks in women: preterm delivery and increased susceptibility to contract HIV. Both incidences kill millions of newborns and adults annually. Therefore, it is urgent to study the cause of BV, because discovering its cause will be a key step in developing more effective ways to prevent and cure the disease. In healthy women, lactobacilli dominate the vaginal microbial ecology. During BV, a shift in microbial dominance occurs-lactobacilli decrease while Gardnerrella vaginalis and anaerobic bacteria increase It is unknown, however, what triggers the shift in vaginal ecology to cause BV. We have isolated phages that infect vaginal lactobacilli. Because these phages can potentially shift vaginal microbial dominance, they are implicated as an underlying cause for BV. We hypothesize that BV may occur after phages infect vaginal lactobacilli. We will test this hypothesis according to Koch's postulates. Namely, a virus isolated from lactobacilli will be inoculated into an animal to cause BV in the animal. We will achieve two specific aims: 1) Study in vitro interactions between phages and monkey vaginal lactobacilli. 2) Establish a monkey BV model by shifting vaginal ecology with a Lactobacillus phage. Upon completion of the study, we expect to have developed a BV animal model based on Koch's postulates, documented that BV can be an infectious disease and that the infectious pathogen is the Lactobacillus phage. We will have an improved understanding of the BV etiology. This will be the first step in attaining our long-term goal: developing better methods to treat and prevent BV.

本申请是为了响应题为“微生物相互作用对传染病的影响”的 NIH RFA (AI-02-008)。具体来说，我们将研究动物实验性细菌性阴道病（BV）发展过程中病毒（噬菌体）和阴道乳酸杆菌之间的相互作用。 BV 是影响全世界女性的最常见的阴道疾病。由于病因不明，没有方法可以预防 BV。虽然细菌性阴道炎本身只有轻微的不适，例如分泌物和鱼腥味，但细菌性阴道炎与女性的两大健康风险有关：早产和感染艾滋病毒的可能性增加。这两种事件每年都会导致数百万新生儿和成人死亡。因此，研究BV的病因刻不容缓，因为找到其病因将是开发更有效的方法来预防和治疗该疾病的关键一步。 在健康女性中，乳酸菌在阴道微生物生态中占主导地位。 BV期间，微生物优势发生转变——乳酸杆菌减少，而阴道加德纳菌和厌氧菌增加。然而，尚不清楚是什么引发了阴道生态的转变，导致BV。我们分离出感染阴道乳酸杆菌的噬菌体。由于这些噬菌体可能会改变阴道微生物的优势，因此它们被认为是 BV 的根本原因。我们推测BV可能是噬菌体感染阴道乳酸杆菌后发生的。我们将根据科赫假设来检验这个假设。即，将从乳酸杆菌中分离出的病毒接种到动物体内，从而在动物中引起BV。我们将实现两个具体目标： 1）研究噬菌体与猴阴道乳酸杆菌之间的体外相互作用。 2) 通过乳酸菌噬菌体改变阴道生态建立猴 BV 模型。 研究完成后，我们预计将开发出基于 Koch 的 BV 动物模型 假设，记录表明 BV 可以是一种传染病，传染性病原体是乳杆菌噬菌体。我们将对 BV 病因学有更深入的了解。这将是实现我们长期目标的第一步：开发更好的方法来治疗和预防 BV。