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).