Abstract:
:Bacterial 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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Lee CY,Cheu RK,Lemke MM,Gustin AT,France MT,Hampel B,Thurman AR,Doncel GF,Ravel J,Klatt NR,Arnold KBdoi
10.1038/s41467-020-19880-wsubject
Has Abstractpub_date
2020-12-01 00:00:00pages
6147issue
1issn
2041-1723pii
10.1038/s41467-020-19880-wjournal_volume
11pub_type
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