Viral Infection in Lactobacilli: An Animal BV Model

该申请是对NIH RFA （AI-02-008）题为“微生物相互作用对传染病的影响”的回应。具体来说，我们将研究动物细菌性阴道病（BV）发生过程中病毒（噬菌体）与阴道乳酸菌的相互作用。细菌性阴道炎是影响全世界女性的最常见的阴道疾病。由于病因不明，目前尚无预防细菌性阴道炎的方法。虽然细菌性阴道炎本身只有轻微的不适，如分泌物和腥味，但细菌性阴道炎与妇女的两大健康风险有关：早产和增加感染艾滋病毒的易感性。这两种疾病每年导致数百万新生儿和成年人死亡。因此，迫切需要研究细菌性阴道炎的病因，因为发现其病因将是制定更有效的预防和治疗方法的关键一步。

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.