title: Unique Insights in the Cervicovaginal Lactobacillus iners and L. crispatus Proteomes and Their Associations with Microbiota Dysbiosis.
abstract: BACKGROUND
  A Lactobacillus-dominated cervicovaginal microbiota (VMB) protects women from adverse reproductive health outcomes, but the role of L. iners in the VMB is poorly understood. Our aim was to explore the association between the cervicovaginal L. iners and L. crispatus proteomes and VMB composition.
  
  
  METHODS
  The vaginal proteomes of 50 Rwandan women at high HIV risk, grouped into four VMB groups (based on 16S rDNA microarray results), were investigated by mass spectrometry using cervicovaginal lavage (CVL) samples. Only samples with positive 16S results for L. iners and/or L. crispatus within each group were included in subsequent comparative protein analyses: Lactobacillus crispatus-dominated VMB cluster (with 16S-proven L. iners (ni) = 0, and with 16S-proven L. crispatus (nc) = 5), L. iners-dominated VMB cluster (ni = 11, nc = 4), moderate dysbiosis (ni = 12, nc = 2); and severe dysbiosis (ni = 8, nc = 2). The relative abundances of proteins that were considered specific for L. iners and L. crispatus were compared among VMB groups.
  
  
  RESULTS
  Forty Lactobacillus proteins were identified of which 7 were specific for L. iners and 11 for L. crispatus. The relative abundances of L. iners DNA starvation/stationary phase protection protein (DPS), and the glycolysis enzymes glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glucose-6-phosphate isomerase (GPI), were significantly decreased in women with L. iners-containing dysbiosis compared to women with a L. iners-dominated VMB, independent of vaginal pH and L. iners abundance. Furthermore, L. iners DPS, GAPDH, GPI, and fructose-bisphosphate aldolase (ALDO) were significantly negatively associated with vaginal pH. Glycolysis enzymes of L. crispatus showed a similar negative, but nonsignificant, trend related to dysbiosis.
  
  
  CONCLUSIONS
  Most identified Lactobacillus proteins had conserved intracellular functions, but their high abundance in CVL supernatant might imply an additional extracellular (moonlighting) role. Our findings suggest that these proteins can be important in maintaining a Lactobacillus-dominated VMB. Functional studies are needed to investigate their roles in vaginal bacterial communities and whether they can be used to prevent vaginal dysbiosis.
authors.affiliation: Amsterdam Institute for Global Health and Development (AIGHD) and Department of Global Health, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Hanneke
authors.initials: H
authors.lastname: Borgdorff
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Armstrong
authors.affiliation: Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.|Centre of Microbial and Plant Genetics, Catholic University Leuven, Leuven, Belgium.|Laboratory of Environmental Ecology and Applied Microbiology, University of Antwerp, Antwerp, Belgium.
authors.forename: Hanne L P
authors.initials: HL
authors.lastname: Tytgat
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Dong
authors.initials: D
authors.lastname: Xia
authors.affiliation: Rinda Ubuzima, Kigali, Rwanda.
authors.forename: Gilles F
authors.initials: GF
authors.lastname: Ndayisaba
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.|Faculty of Natural Sciences, Keele University, Keele, United Kingdom.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Wastling
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.|Rinda Ubuzima, Kigali, Rwanda.
authors.forename: Janneke H H M
authors.initials: JH
authors.lastname: van de Wijgert
mesh_terms: D000328:Adult; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002584:Cervix Uteri / Q000382:microbiology*; D004269:DNA, Bacterial / Q000235:genetics; D064806:Dysbiosis / Q000378:metabolism* / Q000382:microbiology; D005260:Female; D006801:Humans; D007778:Lactobacillus / Q000235:genetics / Q000378:metabolism*; D064307:Microbiota; D008875:Middle Aged; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D012329:RNA, Bacterial / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D014621:Vagina / Q000382:microbiology*
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D020543:Proteome; D012329:RNA, Bacterial; D012336:RNA, Ribosomal, 16S