The N-terminal domain of the R28 protein promotes emm28 group A Streptococcus adhesion to host cells via direct binding to three integrins

The Journal of Biological Chemistry
Antonin WeckelAgnès Fouet

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 event...Continue Reading

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Citations

Dec 11, 2019·Proceedings of the National Academy of Sciences of the United States of America·Fiona WhelanJennifer R Potts
Jun 7, 2020·Archives of Microbiology·Munazza IjazGhulam Murtaza
Dec 16, 2020·The Journal of Clinical Investigation·Antonin WeckelAgnès Fouet
Jan 12, 2021·Frontiers in Microbiology·Cinthia Alves-BarrocoAlexandra R Fernandes
Jan 20, 2021·The Journal of Clinical Investigation·Romain Deshayes de CambronneJulie Guignot
Apr 15, 2020·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·K Gröndahl-Yli-HannukselaJ Vuopio
Apr 7, 2021·Infection and Immunity·Roshika RoshikaPaul Sumby

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