Abstract
Group A Streptococcus (GAS) is a human-specific pathogen responsible for a wide range of diseases, ranging from superficial to life-threatening invasive infections, including endometritis, and autoimmune sequelae. GAS strains express a vast repertoire of virulence factors that varies depending on the strain genotype, and many adhesin proteins that enable GAS to adhere to host cells are restricted to some genotypes. GAS emm28 is the third most prevalent genotype in invasive infections in France and is associated with gyneco-obstetrical infections. emm28 strains harbor R28, a cell wall-anchored surface protein that has previously been reported to promote adhesion to cervical epithelial cells. Here, using cellular and biochemical approaches, we sought to determine whether R28 supports adhesion also to other cells and to characterize its cognate receptor. We show that through its N-terminal domain, R28Nt, R28 promotes bacterial adhesion to both endometrial-epithelial and endometrial-stromal cells. R28Nt was further subdivided into two domains, and we found that both are involved in cell binding. R28Nt and both subdomains interacted directly with the laminin-binding α3β1, α6β1, and α6β4 integrins; interestingly, these bindings events did not require divalent cations. R28 is the first GAS adhesin reported to bind directly to integrins that are expressed in most epithelial cells. Finally, R28Nt also promoted binding to keratinocytes and pulmonary epithelial cells, suggesting that it may be involved in supporting the prevalence in invasive infections of the emm28 genotype.
Highlights
Group A Streptococcus (GAS) is a human-specific pathogen responsible for a wide range of diseases, ranging from superficial to life-threatening invasive infections, including endometritis, and autoimmune sequelae
The first to third most prevalent genotype in Europe, emm28, is responsible for 8% of GAS invasive infections in France [9, 10, 34]. It is associated with endometritis, and for example, in France, 27% of GAS invasive infections in women occur in the gyneco-obstetrical sphere (10 –13). emm28 strains harbor an integrative conjugative element named RD2 that was likely horizontally transferred from Streptococcus agalactiae, known as group B Streptococcus (GBS) [13, 14]
To assay the role of R28 in a more physiological situation, we tested whether the phenotype could be observed on human decidual stromal cells isolated from decidual biopsy of specimens obtained after caesarian delivery (Fig. 2A)
Summary
X Antonin Weckel‡§¶, Dorian Ahamada‡§¶, Samuel Bellais‡§¶1, Céline Méhats‡§¶, Céline Plainvert‡§¶ʈ**, Magalie Longo‡§¶, Claire Poyart‡§¶ʈ**, and X Agnès Fouet‡§¶ʈ2 From the ‡INSERM U1016, Institut Cochin, §CNRS UMR 8104, and ¶Université Paris Descartes, UMR-S1016 Paris, France and the ʈCentre National de Référence des Streptocoques and the **Hôpitaux Universitaires Paris Centre, Institut Cochin, Assistance Publique Hôpitaux de Paris, 75014 Paris, France
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