Understanding the patterns of within-host genetic variation of pathogens is a new frontier in molecular epidemiology and infectious disease biology. By tracing the relationship of closely-related clonal strains using mutations that have occurred after introduction of a bacterium to its human host, we can detect spatial structuring, adaptive evolution and recombination, leading to a deeper picture of the infection process. Our focus in this project is to determine whether Chlamydia trachomatis (Ct), an important obligate intracellular bacterium that is responsible for over 131 million cases of sexually-transmitted infections globally each year, disseminates between the rectum and endocervix of infected women. Understanding within-host movement of Ct will be important for designing future strategies to study transmission and, importantly, will provide initial knowledge of the cycle of transmission within the host and whether rectal infections are being spread to the endocervix. This is important because treatment of endocervical infections has been shown to be inadequate for eliminating infection in the rectum. In addition, this cycle of transmission would be detrimental in terms of the increased risk of upper genital tract sequelae and transmission to partners. We will use samples from a study site in Fiji that has a population of young women with an unusually high rate of Ct infection (up to 38%) allowing us access to a relatively large number the subjects with multiple body site infections.
In Aim 1 we will select 25 women with viable Ct infections in the endocervix, vagina and rectum for genomic sequencing to determine Ct genomic strain type composition at each anatomic site. Based on these results, in Aim 2 we will sequence 10 clones from each site for 20 women simultaneously infected in the rectum and genital tract, reconstruct whether admixture of Ct between the sites occurred, and estimate relative bottleneck sizes. This innovative study will provide the first data of its kind on elucidating within-host Ct transmission dynamics that will be important for selecting optimal body sites for diagnostic screening and for determining appropriate therapeutic regimens.
Chlamydia trachomatis is the leading bacterial cause of sexually transmitted infections (STIs) in the world today. Rates of rectal infections are increasing among heterosexual women in many countries but we have little knowledge regarding transmission from the endocervix to the rectum or vice versa, which is important because rectal infections require a longer therapeutic regimen to eradicate than endocervical infection; inadequate treatment can result in a cycle of transmission within the host that can be detrimental in terms of sequelae but also represent a higher risk of transmission to partners. We will use the resolving power of genome sequencing to determine whether C. trachomatis has simultaneously or at different times infected the rectum and endocervix and the dynamics of within host transmission.
