Vaginal microbial dynamics and pathogen colonization in a humanized microbiota mouse model.

Marlyd E Mejia, Vicki Mercado-Evans, Jacob J Zulk, Samantha Ottinger, Korinna Ruiz, Mallory B Ballard, Stephanie W Fowler, Robert A Britton, Kathryn A Patras
Author Information
  1. Marlyd E Mejia: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
  2. Vicki Mercado-Evans: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
  3. Jacob J Zulk: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
  4. Samantha Ottinger: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
  5. Korinna Ruiz: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
  6. Mallory B Ballard: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
  7. Stephanie W Fowler: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA. ORCID
  8. Robert A Britton: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
  9. Kathryn A Patras: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA. katy.patras@bcm.edu. ORCID

Abstract

Vaginal microbial composition is associated with differential risk of urogenital infection. Although Lactobacillus spp. are thought to confer protection against infection, the lack of in vivo models resembling the human vaginal microbiota remains a prominent barrier to mechanistic discovery. Using 16S rRNA amplicon sequencing of C57BL/6J female mice, we found that vaginal microbial composition varies within and between colonies across three vivaria. Noting vaginal microbial plasticity in conventional mice, we assessed the vaginal microbiome of humanized microbiota mice (mice). Like the community structure in conventional mice, mice vaginal microbiota clustered into community state types but, uniquely, mice communities were frequently dominated by Lactobacillus or Enterobacteriaceae. Compared to conventional mice, mice were less susceptible to uterine ascension by urogenital pathobionts group B Streptococcus (GBS) and Prevotella bivia. Although Escherichia and Lactobacillus both correlated with the absence of uterine GBS, vaginal pre-inoculation with exogenous mouse-derived E. coli, but not Ligilactobacillus murinus, reduced vaginal GBS burden. Overall, mice serve as a useful model to elucidate the role of endogenous microbes in conferring protection against urogenital pathogens.

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Grants

  1. T32 GM152777/NIGMS NIH HHS
  2. R25 GM056929/NIGMS NIH HHS
  3. P30 DK056338/NIDDK NIH HHS
  4. U19 AI157981/NIAID NIH HHS
  5. T32 GM136554/NIGMS NIH HHS
  6. R01 DK128053/NIDDK NIH HHS
  7. F31 AI167547/NIAID NIH HHS
  8. F31 HD111236/NICHD NIH HHS
  9. F31 AI167538/NIAID NIH HHS

MeSH Term

Humans
Female
Animals
Mice
RNA, Ribosomal, 16S
Escherichia coli
Mice, Inbred C57BL
Vagina
Microbiota
Disease Models, Animal
Streptococcus agalactiae

Chemicals

RNA, Ribosomal, 16S

Word Cloud

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