Published on December 10, 2018 | Updated on December 11, 2018

VMMTSS Project

Impact of vaginal microbiote on the development of menstrual toxic shock syndrome

Project leaders : Gérard Lina (CIRI) and Claire Prigent-Combaret (EM)

Host commensal microflora are important for health as they can strongly affect the ecology of pathogenic bacteria by preventing the growth of the latter and/or affecting their virulence and, by the way, the occurrence and the severity of infection.
Staphylococcus aureus that composes human normal flora stays one of the leading cause of human infection.
Its physiopathogeny is related to the production of a broad range of virulence factors that includes TSST-1. This toxin is implicated in Toxic Shock Syndrome (TSS), a systemic illness characterized by extensive T-cell proliferation throughout the body that provokes an acute-onset illness called TSS characterized by fever, hypotension, a sunburn-like rash, vomiting, diarrhoea and multiple organs failure. Most reported cases correspond to menstrual TSS (mTSS) and involve young, healthy menstruating women with vaginal colonisation by a S. aureus strain producing TSST-1 and using tampons.
From epidemiological survey on tampon use and vaginal colonisation by S. aureus producing TSST-1, it is known that only a small proportion of women at risk develops mTSS, questioning the role vaginal microflora that may trigger and/or protect against mTSS by controlling the ecology of S. aureus TSST-1+ and its virulence either directly through bacterial interference or indirectly by biochemical modification of the vaginal environment.
To date, they are numerous knowledge gaps regarding the relation between the vaginal microbiote, vaginal environment and mTSS physiopathology, mainly due to the lack of studies on patients colonised by S. aureus TSST-1+ strain and that develop mTSS. We would like to take advantage of the current increase number of mTSS noticed to the CNR des Staphylocoques to investigate how the vaginal microflora controls the occurrence of the disease.
We hypothesize that S. aureus TSST-1+clones responsible of mTSS share a set of genetic characteristics in addition to specific agr alleles that determine their virulence, and that the vaginal microflora may influence the ecology of S. aureus TSST-1+ and its virulence by either directly controlling (positively or negatively) its growth and/or TSST-1 production, or indirectly by modifying the vaginal environmental conditions (i.e. pH, carbon, O2 levels…).
The objects of the project are to (i) identify networks of genetic determinants that characterize S. aureus TSST-1+ clones responsible of mTSS by genomic approach, (ii) to compare the composition of vaginal microbiota between different groups of patients colonised or not with S. aureus TSST-1+ strain that develop or not mTSS and (iii) to determine populations at risk of mTSS from vaginal microbial communities, vaginal fluid biochemical composition, vaginal toxin production and host immune response.
Only an integrative multidisciplinary approach that combines physiopathology, microbial ecology and biostatistics will help to discover new knowledge about the disease, identify women at risk of mTSS and new strategy to prevent mTSS.

Co-leaders : Gérard Lina, team "Pathogenèse des infections à staphylocoques" (CIRI) and Claire Prigent-Combaret, team "Rhizosphère"(EM).
Collaborative partners: Jean Thioulouse, team "Bioinformatique et Génomique Evolutive" (LBBE).
Project duration : 3 years
Financing :
PhD fellowship and consumable money
PhD fellow : Isaline Jacquemond