SpyAD, a moonlighting protein of group A Streptococcus contributing to bacterial division and host cell adhesion.

Marilena Gallotta, Giovanni Gancitano, Giampiero Pietrocola, Marirosa Mora, Alfredo Pezzicoli, Giovanna Tuscano, Emiliano Chiarot, Vincenzo Nardi-Dei, Anna Rita Taddei, Simonetta Rindi, Pietro Speziale, Marco Soriani, Guido Grandi, Immaculada Margarit, Giuliano Bensi

Index: Infect. Immun. 82(7) , 2890-901, (2014)

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Abstract

Group A streptococcus (GAS) is a human pathogen causing a wide repertoire of mild and severe diseases for which no vaccine is yet available. We recently reported the identification of three protein antigens that in combination conferred wide protection against GAS infection in mice. Here we focused our attention on the characterization of one of these three antigens, Spy0269, a highly conserved, surface-exposed, and immunogenic protein of unknown function. Deletion of the spy0269 gene in a GAS M1 isolate resulted in very long bacterial chains, which is indicative of an impaired capacity of the knockout mutant to properly divide. Confocal microscopy and immunoprecipitation experiments demonstrated that the protein was mainly localized at the cell septum and could interact in vitro with the cell division protein FtsZ, leading us to hypothesize that Spy0269 is a member of the GAS divisome machinery. Predicted structural domains and sequence homologies with known streptococcal adhesins suggested that this antigen could also play a role in mediating GAS interaction with host cells. This hypothesis was confirmed by showing that recombinant Spy0269 could bind to mammalian epithelial cells in vitro and that Lactococcus lactis expressing Spy0269 on its cell surface could adhere to mammalian cells in vitro and to mice nasal mucosa in vivo. On the basis of these data, we believe that Spy0269 is involved both in bacterial cell division and in adhesion to host cells and we propose to rename this multifunctional moonlighting protein as SpyAD (Streptococcus pyogenes Adhesion and Division protein). Copyright © 2014, American Society for Microbiology. All Rights Reserved.