Defense Date
2026
Document Type
Thesis
Degree Name
Master of Science
Department
Microbiology & Immunology
First Advisor
Myrna G. Serrano
Abstract
Gardnerella is a diverse bacterial genus comprising at least thirteen genomically distinct species that colonize the vaginal microbiome and are strongly associated with bacterial vaginosis. The Copper intrauterine device (Copper IUD) is widely used for contraception, yet its effects on individual Gardnerella species remain poorly characterized, and the mechanisms by which copper ions released from the device may influence Gardnerella ecology are unknown. This thesis investigated the copper-Gardnerella relationship across three complementary dimensions: longitudinal epidemiological analysis, in vitro growth kinetics, and comparative genomics.
In the epidemiological analysis, whole metagenome shotgun sequencing data from 149 sub-Saharan African women enrolled in the ECHO trial were analyzed across three contraceptive arms: Copper IUD, depot medroxyprogesterone acetate intramuscular injection (DMPA-IM), and levonorgestrel subdermal implant, at three time points: Baseline, Month 1, and Month 3. Centered log-ratio transformed species abundance was modelled using Gaussian linear mixed models with two-stage Benjamini-Hochberg correction. No contraceptive method produced statistically robust shifts in overall Gardnerella community composition, species richness, or individual species abundance after correction for multiple comparisons. However, Copper IUD users exhibited significantly higher dominant species transition rates from Month 1 to Month 3 relative to LNG Implant users (BH-adjusted p = 0.014), and Group 2 (G. picketii/piotti) CLR abundance was significantly higher in Copper IUD versus DMPA-IM at Month 1 (BH-adjusted p = 0.011), suggesting subtle species-specific community instability.
In vitro copper growth curve experiments confirmed that all three Gardnerella isolates tested, G. vaginalis 14018, VM 224, and G. leopoldii AMD, showed clear concentration-dependent growth suppression with near-complete inhibition at approximately 1.0 × 10⁻⁵ g/L, well below the copper concentrations reported in the uterine cavity of Copper IUD users.
Comparative genomic analysis of 177 quality-filtered Gardnerella genomes revealed that copper gene repertoire is shaped primarily by isolation source and vaginolysin status rather than taxonomic identity. Gastrointestinal isolates and vaginolysin-negative genomes carried significantly more copper-associated genes, with a highly significant interaction between these predictors concentrating copper gene enrichment in vaginolysin-negative gastrointestinal strains.
Collectively, these findings support a model in which Copper IUD effects on vaginal Gardnerella ecology are mediated primarily through indirect community-level perturbations rather than direct copper toxicity to Gardnerella and demonstrate that copper resistance is not a species-level trait in this genus.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-7-2026