title: Comparative genomics of Lactobacillus crispatus suggests novel mechanisms for the competitive exclusion of Gardnerella vaginalis.
abstract: BACKGROUND
  Lactobacillus crispatus is a ubiquitous micro-organism encountered in a wide range of host-associated habitats. It can be recovered from the gastrointestinal tract of animals and it is a common constituent of the vaginal microbiota of humans. Moreover, L. crispatus can contribute to the urogenital health of the host through competitive exclusion and the production of antimicrobial agents. In order to investigate the genetic diversity of this important urogenital species, we performed a comparative genomic analysis of L. crispatus.
  
  
  RESULTS
  Utilizing the completed genome sequence of a strain ST1 and the draft genome sequences of nine other L. crispatus isolates, we defined the scale and scope of the pan- and core genomic potential of L. crispatus. Our comparative analysis identified 1,224 and 2,705 ortholog groups present in all or only some of the ten strains, respectively. Based on mathematical modeling, sequencing of additional L. crispatus isolates would result in the identification of new genes and functions, whereas the conserved core of the ten strains was a good representation of the final L. crispatus core genome, estimated to level at about 1,116 ortholog groups. Importantly, the current core was observed to encode bacterial components potentially promoting urogenital health. Using antibody fragments specific for one of the conserved L. crispatus adhesins, we demonstrated that the L. crispatus core proteins have a potential to reduce the ability of Gardnerella vaginalis to adhere to epithelial cells. These findings thereby suggest that L. crispatus core proteins could protect the vagina from G. vaginalis and bacterial vaginosis.
  
  
  CONCLUSIONS
  Our pan-genome analysis provides insights into the intraspecific genome variability and the collective molecular mechanisms of the species L. crispatus. Using this approach, we described the differences and similarities between the genomes and identified features likely to be important for urogenital health. Notably, the conserved genetic backbone of L. crispatus accounted for close to 60% of the ortholog groups of an average L. crispatus strain and included factors for the competitive exclusion of G. vaginalis, providing an explanation on how this urogenital species could improve vaginal health.
authors.affiliation: Institute of Biotechnology, University of Helsinki, Viikinkaari 4, PO Box 56, FI-00014 Helsinki, Finland. teija.ojala@helsinki.fi.
authors.forename: Teija
authors.initials: T
authors.lastname: Ojala
authors.forename: Matti
authors.initials: M
authors.lastname: Kankainen
authors.forename: Joana
authors.initials: J
authors.lastname: Castro
authors.forename: Nuno
authors.initials: N
authors.lastname: Cerca
authors.forename: Sanna
authors.initials: S
authors.lastname: Edelman
authors.forename: Benita
authors.initials: B
authors.lastname: Westerlund-Wikström
authors.forename: Lars
authors.initials: L
authors.lastname: Paulin
authors.forename: Liisa
authors.initials: L
authors.lastname: Holm
authors.forename: Petri
authors.initials: P
authors.lastname: Auvinen
mesh_terms: D000898:Antibiosis / Q000235:genetics*; D001422:Bacterial Adhesion / Q000235:genetics; D001435:Bacteriophages; D002473:Cell Wall / Q000378:metabolism; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D019295:Computational Biology; D005260:Female; D006194:Gardnerella vaginalis / Q000235:genetics*; D023061:Gene Order; D022761:Gene Transfer, Horizontal; D014644:Genetic Variation; D016680:Genome, Bacterial; D023281:Genomics; D006367:HeLa Cells; D006801:Humans; D007778:Lactobacillus / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D053858:Metabolic Networks and Pathways; D058977:Molecular Sequence Annotation; D005810:Multigene Family; D010802:Phylogeny; D011135:Polysaccharides, Bacterial / Q000378:metabolism
chemical_list: D011135:Polysaccharides, Bacterial