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.
| Gravett, Michael G; Jin, Ling; Pavlova, Sylvia I et al. (2012) Lactobacillus and Pediococcus species richness and relative abundance in the vagina of rhesus monkeys (Macaca mulatta). J Med Primatol 41:183-90 |
| Jin, L; Tao, L; Pavlova, S I et al. (2007) Species diversity and relative abundance of vaginal lactic acid bacteria from women in Uganda and Korea. J Appl Microbiol 102:1107-15 |
