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Models of Murine Vaginal Colonization by Anaerobically Grown Bacteria
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Vaginal microbial dynamics and pathogen colonization in a humanized microbiota mouse model.

Marlyd E Mejia1, Vicki Mercado-Evans1,2, Jacob J Zulk1

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Summary

Humanized microbiota mice (HMb mice) offer a new model for studying vaginal infections. These HMb mice show reduced susceptibility to urogenital pathogens, aiding research into microbial protection.

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Area of Science:

  • Microbiology
  • Immunology
  • Infectious Diseases

Background:

  • Vaginal microbial composition influences urogenital infection risk.
  • Lactobacillus species are believed to protect against infection.
  • A lack of in vivo models hinders mechanistic studies of the human vaginal microbiota.

Purpose of the Study:

  • To assess the utility of humanized microbiota mice (HMb mice) as a model for studying vaginal microbial dynamics and host-pathogen interactions.
  • To investigate the susceptibility of HMb mice to urogenital pathobionts compared to conventional mice.

Main Methods:

  • 16S rRNA amplicon sequencing was used to characterize vaginal microbial composition in C57BL/6J female mice across different colonies and in HMb mice.
  • HMb mice and conventional mice were challenged with urogenital pathobionts, including group B Streptococcus (GBS) and Prevotella bivia.
  • The effect of pre-inoculation with specific bacterial species (E. coli, Ligilactobacillus murinus) on pathogen burden was evaluated in HMb mice.

Main Results:

  • Vaginal microbial composition varied within and between mouse colonies.
  • HMb mice exhibited distinct community state types, often dominated by Lactobacillus or Enterobacteriaceae.
  • HMb mice demonstrated reduced susceptibility to uterine ascension of GBS and Prevotella bivia compared to conventional mice.
  • Exogenous E. coli, but not Ligilactobacillus murinus, reduced vaginal GBS burden in HMb mice.
  • Escherichia and Lactobacillus species correlated with the absence of uterine GBS.

Conclusions:

  • HMb mice represent a valuable in vivo model for investigating the protective roles of endogenous vaginal microbes against urogenital pathogens.
  • This model facilitates mechanistic discovery regarding microbial communities and their impact on infection susceptibility.
  • Understanding the interplay between specific microbes like Lactobacillus and Enterobacteriaceae is crucial for developing strategies against urogenital infections.