Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract

Alexander S. Zevin, Irene Y. Xie, Kenzie Birse, Kelly Arnold, Laura Romas, Garrett Westmacott, Richard M. Novak, Stuart McCorrister, Lyle R. McKinnon, Craig R. Cohen, Romel Mackelprang, Jairam Lingappa, Doug A. Lauffenburger, Nichole Klatt, Adam D. Burgener

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

The mechanism(s) by which bacterial communities impact susceptibility to infectious diseases, such as HIV, and maintain female genital tract (FGT) health are poorly understood. Evaluation of FGT bacteria has predominantly been limited to studies of species abundance, but not bacterial function. We therefore sought to examine the relationship of bacterial community composition and function with mucosal epithelial barrier health in the context of bacterial vaginosis (BV) using metaproteomic, metagenomic, and in vitro approaches. We found highly diverse bacterial communities dominated by Gardnerella vaginalis associated with host epithelial barrier disruption and enhanced immune activation, and low diversity communities dominated by Lactobacillus species that associated with lower Nugent scores, reduced pH, and expression of host mucosal proteins important for maintaining epithelial integrity. Importantly, proteomic signatures of disrupted epithelial integrity associated with G. vaginalis-dominated communities in the absence of clinical BV diagnosis. Because traditional clinical assessments did not capture this, it likely represents a larger underrepresented phenomenon in populations with high prevalence of G. vaginalis. We finally demonstrated that soluble products derived from G. vaginalis inhibited wound healing, while those derived from L. iners did not, providing insight into functional mechanisms by which FGT bacterial communities affect epithelial barrier integrity.

Original languageEnglish (US)
Article numbere1005889
JournalPLoS Pathogens
Volume12
Issue number9
DOIs
StatePublished - Sep 1 2016
Externally publishedYes

Fingerprint

Gardnerella vaginalis
Microbiota
Wound Healing
Bacterial Vaginosis
Metagenomics
Health
Lactobacillus
Proteomics
Communicable Diseases
HIV
Bacteria
Population
Proteins

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Zevin, A. S., Xie, I. Y., Birse, K., Arnold, K., Romas, L., Westmacott, G., ... Burgener, A. D. (2016). Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract. PLoS Pathogens, 12(9), [e1005889]. https://doi.org/10.1371/journal.ppat.1005889

Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract. / Zevin, Alexander S.; Xie, Irene Y.; Birse, Kenzie; Arnold, Kelly; Romas, Laura; Westmacott, Garrett; Novak, Richard M.; McCorrister, Stuart; McKinnon, Lyle R.; Cohen, Craig R.; Mackelprang, Romel; Lingappa, Jairam; Lauffenburger, Doug A.; Klatt, Nichole; Burgener, Adam D.

In: PLoS Pathogens, Vol. 12, No. 9, e1005889, 01.09.2016.

Research output: Contribution to journalArticle

Zevin, AS, Xie, IY, Birse, K, Arnold, K, Romas, L, Westmacott, G, Novak, RM, McCorrister, S, McKinnon, LR, Cohen, CR, Mackelprang, R, Lingappa, J, Lauffenburger, DA, Klatt, N & Burgener, AD 2016, 'Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract', PLoS Pathogens, vol. 12, no. 9, e1005889. https://doi.org/10.1371/journal.ppat.1005889
Zevin, Alexander S. ; Xie, Irene Y. ; Birse, Kenzie ; Arnold, Kelly ; Romas, Laura ; Westmacott, Garrett ; Novak, Richard M. ; McCorrister, Stuart ; McKinnon, Lyle R. ; Cohen, Craig R. ; Mackelprang, Romel ; Lingappa, Jairam ; Lauffenburger, Doug A. ; Klatt, Nichole ; Burgener, Adam D. / Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract. In: PLoS Pathogens. 2016 ; Vol. 12, No. 9.
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