A systematic and functional classification of Streptococcus pyogenes that serves as a new tool for molecular typing and vaccine development.

Sanderson-Smith M1, De Oliveira DM1, Guglielmini J2, McMillan DJ3, Vu T4, Holien JK5, Henningham A6, Steer AC7, Bessen DE8, Dale JB9, Curtis N10, Beall BW11, Walker MJ6, Parker MW12, Carapetis JR13, Van Melderen L14, Sriprakash KS15, Smeesters PR16; M Protein Study Group.

Abstract

Streptococcus pyogenes ranks among the main causes of mortality from bacterial infections worldwide. Currently there is no vaccine to prevent diseases such as rheumatic heart disease and invasive streptococcal infection. The streptococcal M protein that is used as the substrate for epidemiological typing is both a virulence factor and a vaccine antigen. Over 220 variants of this protein have been described, making comparisons between proteins difficult, and hindering M protein-based vaccine development. A functional classification based on 48 emm-clusters containing closely related M proteins that share binding and structural properties is proposed. The need for a paradigm shift from type-specific immunity against S. pyogenes to emm-cluster based immunity for this bacterium should be further investigated. Implementation of this emm-cluster-based system as a standard typing scheme for S. pyogenes will facilitate the design of future studies of M protein function, streptococcal virulence, epidemiological surveillance, and vaccine development.