Comparative genomics of Gardnerella vaginalis strains reveals substantial differences in metabolic and virulence potential

Abstract

Background: Gardnerella vaginalis is described as a common vaginal bacterial species whose presence correlates strongly with bacterial vaginosis (BV). Here we report the genome sequencing and comparative analyses of three strains of G. vaginalis. Strains 317 (ATCC 14019) and 594 (ATCC 14018) were isolated from the vaginal tracts of women with symptomatic BV, while Strain 409-05 was isolated from a healthy, asymptomatic individual with a Nugent score of 9.

Principal findings: Substantial genomic rearrangement and heterogeneity were observed that appeared to have resulted from both mobile elements and substantial lateral gene transfer. These genomic differences translated to differences in metabolic potential. All strains are equipped with significant virulence potential, including genes encoding the previously described vaginolysin, pili for cytoadhesion, EPS biosynthetic genes for biofilm formation, and antimicrobial resistance systems, We also observed systems promoting multi-drug and lantibiotic extrusion. All G. vaginalis strains possess a large number of genes that may enhance their ability to compete with and exclude other vaginal colonists. These include up to six toxin-antitoxin systems and up to nine additional antitoxins lacking cognate toxins, several of which are clustered within each genome. All strains encode bacteriocidal toxins, including two lysozyme-like toxins produced uniquely by strain 409-05. Interestingly, the BV isolates encode numerous proteins not found in strain 409-05 that likely increase their pathogenic potential. These include enzymes enabling mucin degradation, a trait previously described to strongly correlate with BV, although commonly attributed to non-G. vaginalis species.

Conclusions: Collectively, our results indicate that all three strains are able to thrive in vaginal environments, and therein the BV isolates are capable of occupying a niche that is unique from 409-05. Each strain has significant virulence potential, although genomic and metabolic differences, such as the ability to degrade mucin, indicate that the detection of G. vaginalis in the vaginal tract provides only partial information on the physiological potential of the organism.

Figure 1. Bifidobacteriaceae phylogeny.

Maximum likelihood 16S rDNA based phylogentic reconstruction of the Bifidobacteriaceae. Bootstrap values less than 100 are shown at each node. Larger taxonomic clusters have been collapsed for clarity.

Figure 2. Genome atlases.

Genome atlases of the two G. vaginalis strains with completed genome sequences: 409-05 (left) and 317 (right). From outside to inside the circles illustrate ORFs of the ‘+’ (1) and ‘−’ (2) strands, GC Skew (3) and % AT (4).

Figure 3. Orthologue distribution.

Venn diagram showing the number of orthologues shared between the three strains of G. vaginalis.

Figure 4. Genome Synteny.

Overall synteny between G. vaginalis strain 317 (top) and strain 409-05 (bottom). Best Blastn alignments are indicated by a red (same strand) or blue (opposite strand) line and indicate 40–100% ID (illustrated by the light to dark nature of the lines, respectively) over a minimum of 125 contiguous bp. ORFs of the ‘+’ (above) and ‘−’ (below) strands are indicated surrounding the strain and contig information.

Figure 5. Metabolic potential.

The metabolic pathways of G. vaginalis were mapped based upon genome information using iPath. Common pathways are shown (green), along with those specific to strain 409-05 (blue), 317 (orange) and 594 (yellow). Those pathways common to the two BV-isolates are shown in red, while those common to strain 409-05 and 317 are shown in purple. No enzymes were exclusively found in 409-05 and 594.