University of North Carolina at Chapel Hill Graduate School
Doi
Abstract
N. gonorrhoeae is a strictly human pathogen responsible for 100 million infections annually. Infections are typically localized to the lower genital tract in women, but when left untreated, infections can ascend to the upper genital tract leading to a number of health complications including pelvic inflammatory disease and infertility. Despite a localized inflammatory response, individuals do not develop an effective adaptive immune response to the bacteria and remain susceptible to repeated infection. Surprisingly, a large proportion of N. gonorrhoeae infections are carried asymptomatically and women are more likely than men to carry asymptomatic infections. Women with bacterial vaginosis (BV), which is characterized by a shift in the cervicovaginal microbiome to a polymicrobial dysbiosis, are associated with an increased risk of acquiring and transmitting STIs. Studies examining the impact of the vaginal microbiome on basal inflammatory states reported that women with BV were associated with higher expression levels of pro-inflammatory cytokines when compared to BV-negative women. Taken together, these data suggest that variations in vaginal microbial diversity can influence disease susceptibly and/or presentation. We conducted a pilot study to assess differences in the cervicovaginal microbial community of patients presenting to a sexually transmitted infections (STI) clinic with symptomatic vs. asymptomatic N. gonorrhoeae infections. Specimens collected from asymptomatic individuals with N. gonorrhoeae infection and no co-infection with Chlamydia trachomatis and/or Trichomonas vaginalis carried Lactobacillus-dominant microbial communities more frequently than symptomatic patients without co-infection. When compared to asymptomatic individuals, symptomatic women had microbial communities characterized by more diverse and heterogenous bacterial taxa, typically associated with bacterial vaginosis (BV). We utilized a murine model of N. gonorrhoeae infection in which mice pre-colonized with Lactobacillus crispatus to test whether pre-existing L. crispatus was protective from N. gonorrhoeae colonization or whether N. gonorrhoeae infection could drive the loss of L. crispatus during infection. Vaginal infection with either N. gonorrhoeae strain 1291 or an isogenic mutant known to exhibit lower inflammatory had no impact on Lactobacillus burden recovered from the mice. These data taken together suggest that Lactobacillus-dominant vaginal microbial community may protect individuals from developing symptoms during lower genital tract infection with N. gonorrhoeae. Doctor of Philosoph
