National Center for Scientific Research (CNRS), Institute MIVEGEC, 911 Av Agropolis, 34394 Montpellier, France

MINERVA project

Bacterial vaginosis (BV) is a polymicrobial syndrome that modifies vaginal secretions and increases risks of reproductive complications and most sexually transmissible infections. This syndrome is associated with a shift in vaginal microbiota composition from lactic-acid producing bacteria to specific bacterial communities. Concomitant with such shift, sialidases can be detected in vaginal secretions where they release sialic acids (SA), sugar molecules that some bacteria can use as a nutrient source and to escape host’s immunity. While the presence of sialidases is used as a BV diagnosis method, we still know little about SA metabolism in the species associated with BV, and even less about SA-related interactions in the community. The MINERVA project directly addresses this question with the ultimate aim of understanding the role of SA metabolism in the transition from health to disease. I focus my research on the three most prevalent BV-associated bacteria: Gardnerella vaginalis, Prevotella bivia and Atopobium vaginae. First, I investigate the genomic organization and distribution of the genes involved in SA metabolism. Second, I will link these genotypes to phenotypes by experimentally assessing the expression of those genes in clinical samples from BV-positive and negative women. Third, I assess the evolutionary stability of SA metabolism genes and bring insight into the respective roles of SA availability and host’s immune system in the evolution of bacterial SA metabolism. Finally, I create ex-vivo minimal model communities of BV bacteria and examine the ecological interactions between species. By going beyond a taxonomic description to better understand eco-evolutionary functioning, this project will expand our view of the BV microbiome both at the species level, examining in particular intraspecies diversity in genetic composition and expression, and at the community level through the investigation of SA-related interactions.

Main objectives

This project aims at elucidating the function and eco-evolutionary dynamics of sialic acid metabolism in the vaginal microbiome. Combining species- and community-level approaches, it will significantly advance our vision of the role of metabolic diversity and biotic interactions in the transition from health to disease. The project relies on the balance of low-risk, high-gain studies (workpackages WP 1 and 2) and more prospective procedures (WP 3 and 4), with the following specific objectives:

  • WP1. Determine the prevalence and genomic context of genes involved in SA metabolism in BV-associated bacteria.
  • WP2. Experimentally evaluate SA metabolism in BV clinical isolates and characterize intra- and inter-patient diversity.
  • WP3. Investigate the evolutionary history, stability and selective pressures acting on of SA-related genes in bacteria.
  • WP4. Develop an experimental model of minimal BV bacterial community and evaluate the importance of biotic interactions and community context on SA metabolism.

Experimental system

While the bioinformatic part will explore whole vaginal communities with metagenomics (WP1), the experimental parts will focus on three bacterial species: G. vaginalis, A. vaginae and P. bivia, all of which possess putative SA metabolism genes or display sialidase activity. Of note, G. vaginalis is considered the major player in BV, and this bacterium harbours an impressive genetic diversity correlates with sialidase production. G. vaginalis is very often found in combination with A. vaginae and P. bivia and these species can synergistic interact in BV-associated biofilms and for amino-acid metabolism.

Bacterial use of sialic acids in eukaryotic hosts. a) Some bacterial strains produce enzymes called sialidases that release in the environment the sialic acids from the surfaces of host cells. b) Bacterial membranes can be decorated with sialic acids, thereby making the bacteria invisible to the host immune complement. c) Any bacteria with ad hoc transport systems (white arrows) can import free sialic acids, including sialidase producers (blue cells) and non-producers (yellow cells). Sialic acid catabolism provides carbon and energy fueling bacterial growth. d) Biofilm formation is fostered by the presence of sialic acids on bacterial membrane.

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 898796.