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Access Type

WSU Access

Date of Award

January 2022

Degree Type


Degree Name



Biochemistry and Molecular Biology

First Advisor

Robert Akins


Bacterial Vaginosis (BV) is a state of vaginal dysbiosis in which BV-associated species displace the typically dominant species of Lactobacillus. This urogenital disease elevates the risk for complications such as pre-term birth, STDs and HIV. Currently, there is no consensus on the etiology of BV. Standard of care treatment is oral metronidazole; however, therapy has high rates of recurrence. Our previous qPCR study of recurrent BV patients (3+ episodes/year) found strong associations of Gardnerella_Gsp07, G. swidsinksii, and G. leopoldii with refractory and recurrent responses, and a robust recovery of Lactobacillus in remission patients. However, these findings were not applicable across all patients, suggesting the involvement of other microbial organisms. This current research analyzed a subset of the initial recurrent BV patient samples (n = 41), collected before and after oral metronidazole treatment, by next generation sequencing of the V4 domain of the 16S ribosomal RNA. Our research identified a collection of species with diagnostic or prognostic value. Elevated pre-treatment levels of Gardnerella_Gsp07 strongly predicted a refractory response in most patients; however, there were a portion of patients, with a refractory response that had low levels of Gardnerella_Gsp07. As an alternate source of virulence, our data showed high titers of Mageeibacillus indolicus (BVAB3) and P. timonensis. While combinations of low levels of Gardnerella_Gsp07 or Finegoldia magna with high levels of Megasphaera lornae, from the pre-treatment visit, were prognostic for a long-term remission response, Megasphaera lornae, individually, predicted long-term remission with high accuracy. Post-treatment, high levels of Gardnerella, Aerococcus christensenii, A. vaginae, L. jensenii, and Megasphaera_2 combined with lower levels of Megasphaera lornae were prognostic to those who would recur compared to those that would achieve long-term remission. We have proposed a model that offers testable hypotheses about the causes of these clinical responses. Our results have shown indirect evidence of refractory responses being associated with the resistance and/or tolerance to metronidazole by means of sequestration and inactivation. Future direction will involve whole genome shotgun sequencing on a larger set of patient samples to overcome the limited phylogeny of 16S rRNA gene along with potential in vitro experiments and clinical trials to improve drug therapies targeting BV.

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