title: Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract.
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.
authors.affiliation: Department of Pharmaceutics, Washington National Primate Research Center, University of Washington, Seattle, Washington, United States of America.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Zevin
authors.affiliation: National HIV and Retrovirology Labs, JC Wilt Center for Infectious Diseases, Public Health Agency of Canada, Winnipeg, Canada.|Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Canada.
authors.forename: Irene Y
authors.initials: IY
authors.lastname: Xie
authors.affiliation: National HIV and Retrovirology Labs, JC Wilt Center for Infectious Diseases, Public Health Agency of Canada, Winnipeg, Canada.|Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Canada.
authors.forename: Kenzie
authors.initials: K
authors.lastname: Birse
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Kelly
authors.initials: K
authors.lastname: Arnold
authors.affiliation: National HIV and Retrovirology Labs, JC Wilt Center for Infectious Diseases, Public Health Agency of Canada, Winnipeg, Canada.|Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Canada.
authors.forename: Laura
authors.initials: L
authors.lastname: Romas
authors.affiliation: Mass Spectrometry and Proteomics Core, National Microbiology Lab, Public Health Agency of Canada, Winnipeg, Canada.
authors.forename: Garrett
authors.initials: G
authors.lastname: Westmacott
authors.affiliation: Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Richard M
authors.identifier: http://orcid.org/0000-0002-1348-5268
authors.initials: RM
authors.lastname: Novak
authors.affiliation: Mass Spectrometry and Proteomics Core, National Microbiology Lab, Public Health Agency of Canada, Winnipeg, Canada.
authors.forename: Stuart
authors.initials: S
authors.lastname: McCorrister
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Canada.
authors.forename: Lyle R
authors.initials: LR
authors.lastname: McKinnon
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Craig R
authors.initials: CR
authors.lastname: Cohen
authors.affiliation: Department of Global Health, University of Washington, Seattle, Washington, United States of America.
authors.forename: Romel
authors.initials: R
authors.lastname: Mackelprang
authors.affiliation: Department of Global Health, University of Washington, Seattle, Washington, United States of America.|Department of Medicine, University of Washington, Seattle, Washington, United States of America.|Department of Pediatrics, University of Washington, Seattle, Washington, United States of America.
authors.forename: Jairam
authors.initials: J
authors.lastname: Lingappa
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Doug A
authors.initials: DA
authors.lastname: Lauffenburger
authors.affiliation: Department of Pharmaceutics, Washington National Primate Research Center, University of Washington, Seattle, Washington, United States of America.
authors.forename: Nichole R
authors.initials: NR
authors.lastname: Klatt
authors.affiliation: National HIV and Retrovirology Labs, JC Wilt Center for Infectious Diseases, Public Health Agency of Canada, Winnipeg, Canada.|Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Canada.|Unit of Infectious Diseases, Department of Medicine, Center for Molecular Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Burgener