Abstract
Background Bacterial vaginosis (BV) is a prevalent multifactorial disease of women in their reproductive years characterized by a shift from the healthy Lactobacillus sp. dominated microbial community towards a highly diverse anaerobic community. BV can initially be cured by antibiotic therapy in most women, but the high recurrence frequency represents a serious challenge. Moreover, for unknown reasons, a small number of women does not respond to therapy. In a clinical study, out of 37 women diagnosed with BV, 31 were successfully treated with a single peroral dose of metronidazole, while 6 still had BV after treatment. Here, we performed a metatranscriptome analysis of the vaginal microbiota of the subgroup of those non-responding patients (N = 6), comparing them to patients (N = 8) who were successfully treated. Moreover, we followed the changes in the metatranscriptome composition over three months (5 time-points) in patients (N = 2) that developed recurrence in comparison to patients (N = 2) that were permanently cured.
Results In health, Lactobacillus iners and L. crispatus contributed more than 90% of all bacterial transcripts, but they did not co-occur. Their functional profiles in vivo confirmed the pathogenic role of L. iners. In BV, Gardnerella vaginalis contributed on average 37% of all transcripts. In some patients, transcripts from Gardnerella species isolated from the bladder were abundant. In non-responding patients, cas and DNA methyltransferase genes of G. vaginalis were highly up-regulated, suggesting that they might play a role in defense against DNA damaging agents like metronidazole.
Conclusions We hypothesize that colonization by L. iners and re-infection through the bladder contribute to recurrence of BV. Our data suggest that Cas genes of G. vaginalis, in addition to protecting against phages, might be involved in DNA repair thus mitigating the bactericidal effect of DNA damaging agents like metronidazole.
Trial registration: ClinicalTrials.gov NCT02687789. Retrospectively registered on 12 October 2015.