A generalist lifestyle allows rareGardnerellaspp. to persist at low levels in the vaginal microbiome

Abstract

Gardnerella spp. are considered a hallmark of bacterial vaginosis, a dysbiosis of the vaginal microbiome. There are four cpn60 sequence-based subgroups within the genus (A, B, C, and D), and thirteen genome species have been defined recently. Gardnerella spp. co-occur in the vaginal microbiome with varying abundance, and these patterns are shaped by a resource-dependent, exploitative competition, which affects the growth rate of subgroup A, B, and C negatively. The growth rate of rarely abundant subgroup D, however, increases with the increasing number of competitors, negatively affecting the growth rate of others. We hypothesized that a nutritional generalist lifestyle and minimal niche overlap with the other, more abundant Gardnerella spp. facilitate the maintenance of subgroup D in the vaginal microbiome through negative-frequency dependent selection. Using 40 whole genome sequences from isolates representing all four subgroups we found that they could be distinguished based on content of their predicted proteomes. Proteins associated with carbohydrate and amino acid uptake and metabolism were significant contributors to the separation of subgroups. Subgroup D isolates had significantly more of their proteins assigned to amino acid metabolism than the other subgroups. Subgroup D isolates were also significantly different from others in terms of number and type of carbon sources utilized in a phenotypic assay, while the other three could not be distinguished. Overall, the results suggest that a generalist lifestyle and lack of niche overlap with other Gardnerella spp. leads to subgroup D being favoured by negative-frequency dependent selection in the vaginal microbiome.

Population density affects the outcome of competition in co-cultures of Gardnerella species isolated from the human vaginal microbiome

“…Negative frequency-dependent selection favours rare genotypes [1, 2]. Factors like generalist lifestyle, social cheating, and bet hedging, can contribute to the selection of rare genotypes [8, 9, 16–20]. It has been shown that rarely abundant Gardnerella subgroup D are nutritional generalists [8], which may help them to be favoured by negative frequency-dependent selection.…”

“…Factors like generalist lifestyle, social cheating, and bet hedging, can contribute to the selection of rare genotypes [8, 9, 16–20]. It has been shown that rarely abundant Gardnerella subgroup D are nutritional generalists [8], which may help them to be favoured by negative frequency-dependent selection. However, the fact that subgroup D has not been observed to dominate the vaginal microbiome begs the question: if rare subgroup D is favoured by negative frequency-dependent selection, why do not we see microbiomes dominated by subgroup D more often?…”

“…We have shown previously studies that the rare Gardnerella species (subgroup D) have minimal overlap with the other Gardnerella spp. and are probably occupying a different niche in the vagina [8]. As a result, regardless of its competitive ability, if the capacity of subgroup D’s niche is smaller than one of the more common but less competitive subgroups, its abundance will be limited [9, 10, 26].…”

“…Subgroup D isolates were subsequently shown to have a nutritional generalist lifestyle and limited niche overlap with other Gardnerella spp. suggesting that these isolates persist in the vaginal microbiome through negative frequency-dependent selection [8]. Vaginal microbiomes dominated by subgroup D, however, have not been reported [6, 7].…”

Metagenome-validated Parallel Amplicon Sequencing and Text Mining-based Annotations for Simultaneous Profiling of Bacteria and Fungi: Vaginal Microbiome and Mycobiota in Healthy Women

“…Even though the enzymes associated with degradation could not be assigned to a single taxonomy, their exclusivity in these samples already shows an interesting trend. Other studies have discussed inosine in various contexts, including as a metabolite from related intestinal Bi dibacterium pseudolongum that modulates an enhanced immunotherapy response, while for some strains of G. vaginalis it has been indicated as a carbon source [71,72]. These ndings warrant further investigations to understand the role of inosine metabolism among certain G. vaginalis strains within the vaginal ecosystem.…”