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dc.contributor.authorLee, C.Y.
dc.contributor.authorCheu, R.K.
dc.contributor.authorLemke, M.M.
dc.contributor.authorGustin, A.T.
dc.contributor.authorFrance, M.T.
dc.contributor.authorHampel, B.
dc.contributor.authorThurman, A.R.
dc.contributor.authorDoncel, G.F.
dc.contributor.authorRavel, J.
dc.contributor.authorKlatt, N.R.
dc.contributor.authorArnold, K.B.
dc.date.accessioned2021-02-08T20:13:30Z
dc.date.available2021-02-08T20:13:30Z
dc.date.issued2020-12-01
dc.identifier.urihttp://hdl.handle.net/10713/14570
dc.description.abstractBacterial vaginosis is a condition associated with adverse reproductive outcomes and characterized by a shift from a Lactobacillus-dominant vaginal microbiota to a polymicrobial microbiota, consistently colonized by strains of Gardnerella vaginalis. Metronidazole is the first-line treatment; however, treatment failure and recurrence rates remain high. To understand complex interactions between Gardnerella vaginalis and Lactobacillus involved in efficacy, here we develop an ordinary differential equation model that predicts bacterial growth as a function of metronidazole uptake, sensitivity, and metabolism. The model shows that a critical factor in efficacy is Lactobacillus sequestration of metronidazole, and efficacy decreases when the relative abundance of Lactobacillus is higher pre-treatment. We validate results in Gardnerella and Lactobacillus co-cultures, and in two clinical cohorts, finding women with recurrence have significantly higher pre-treatment levels of Lactobacillus relative to bacterial vaginosis-associated bacteria. Overall results provide mechanistic insight into how personalized differences in microbial communities influence vaginal antibiotic efficacy.en_US
dc.description.urihttps://doi.org/10.1038/s41467-020-19880-wen_US
dc.language.isoen_USen_US
dc.publisherNature Springeren_US
dc.relation.ispartofNature communications
dc.subject.meshMetronidazoleen_US
dc.subject.meshModels, Theoreticalen_US
dc.subject.meshVagina--microbiologyen_US
dc.subject.meshVaginosis, Bacterial--drug therapyen_US
dc.subject.meshVaginosis, Bacterial--microbiologyen_US
dc.titleQuantitative modeling predicts mechanistic links between pre-treatment microbiome composition and metronidazole efficacy in bacterial vaginosisen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41467-020-19880-w
dc.identifier.pmid33262350


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