title: The Group A Streptococcus serotype M2 pilus plays a role in host cell adhesion and immune evasion.
abstract: Group A Streptococcus (GAS), or Streptococcus pyogenes, is a human pathogen that causes diseases ranging from skin and soft tissue infections to severe invasive diseases, such as toxic shock syndrome. Each GAS strain carries a particular pilus type encoded in the variable fibronectin-binding, collagen-binding, T antigen (FCT) genomic region. Here, we describe the functional analysis of the serotype M2 pilus encoded in the FCT-6 region. We found that, in contrast to other investigated GAS pili, the ancillary pilin 1 lacks adhesive properties. Instead, the backbone pilin is important for host cell adhesion and binds several host factors, including fibronectin and fibrinogen. Using a panel of recombinant pilus proteins, GAS gene deletion mutants and Lactococcus lactis gain-of-function mutants we show that, unlike other GAS pili, the FCT-6 pilus also contributes to immune evasion. This was demonstrated by a delay in blood clotting, increased intracellular survival of the bacteria in macrophages, higher bacterial survival rates in human whole blood and greater virulence in a Galleria mellonella infection model in the presence of fully assembled FCT-6 pili.
authors.affiliation: Department of Molecular Medicine & Pathology, School of Medical Sciences.|Maurice Wilkins Centre, The University of Auckland, Auckland, New Zealand.
authors.forename: Jia-Yun C
authors.initials: JC
authors.lastname: Tsai
authors.affiliation: Department of Molecular Medicine & Pathology, School of Medical Sciences.|Maurice Wilkins Centre, The University of Auckland, Auckland, New Zealand.
authors.forename: Jacelyn M S
authors.initials: JM
authors.lastname: Loh
authors.affiliation: Department of Molecular Medicine & Pathology, School of Medical Sciences.
authors.forename: Fiona
authors.initials: F
authors.lastname: Clow
authors.affiliation: Department of Molecular Medicine & Pathology, School of Medical Sciences.
authors.forename: Natalie
authors.initials: N
authors.lastname: Lorenz
authors.affiliation: Department of Molecular Medicine & Pathology, School of Medical Sciences.|Maurice Wilkins Centre, The University of Auckland, Auckland, New Zealand.
authors.forename: Thomas
authors.initials: T
authors.lastname: Proft
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism; D000957:Antigens, Viral, Tumor; D001422:Bacterial Adhesion / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D001426:Bacterial Proteins / Q000378:metabolism; D018441:Biofilms; D005353:Fibronectins / Q000378:metabolism; D036781:Fimbriae Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D010861:Fimbriae, Bacterial / Q000378:metabolism; D006801:Humans; D057131:Immune Evasion; D009154:Mutation; D017384:Sequence Deletion; D065288:Serogroup; D013290:Streptococcal Infections / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D014774:Virulence
chemical_list: D018829:Adhesins, Bacterial; D000957:Antigens, Viral, Tumor; D001426:Bacterial Proteins; D005353:Fibronectins; C078635:fibronectin-binding proteins, bacterial; D036781:Fimbriae Proteins