title: Streptococcus pyogenes pili promote pharyngeal cell adhesion and biofilm formation.
abstract: Group A Streptococcus (GAS, Streptococcus pyogenes) is a Gram-positive human pathogen responsible for several acute diseases and autoimmune sequelae that account for half a million deaths worldwide every year. GAS infections require the capacity of the pathogen to adhere to host tissues and assemble in cell aggregates. Furthermore, a role for biofilms in GAS pathogenesis has recently been proposed. Here we investigated the role of GAS pili in biofilm formation. We demonstrated that GAS pilus-negative mutants, in which the genes encoding either the pilus backbone structural protein or the sortase C1 have been deleted, showed an impaired capacity to attach to a pharyngeal cell line. The same mutants were much less efficient in forming cellular aggregates in liquid culture and microcolonies on human cells. Furthermore, mutant strains were incapable of producing the typical three-dimensional layer with bacterial microcolonies embedded in a carbohydrate polymeric matrix. Complemented mutants had an adhesion and aggregation phenotype similar to the wild-type strain. Finally, in vivo expression of pili was indirectly confirmed by demonstrating that most of the sera from human patients affected by GAS-mediated pharyngitis recognized recombinant pili proteins. These data support the role of pili in GAS adherence and colonization and suggest a general role of pili in all pathogenic streptococci.
authors.affiliation: Novartis Vaccines and Diagnostics, Via Fiorentina 1, 53100, Siena, Italy.
authors.forename: Andrea G O
authors.initials: AG
authors.lastname: Manetti
authors.forename: Chiara
authors.initials: C
authors.lastname: Zingaretti
authors.forename: Fabiana
authors.initials: F
authors.lastname: Falugi
authors.forename: Sabrina
authors.initials: S
authors.lastname: Capo
authors.forename: Mauro
authors.initials: M
authors.lastname: Bombaci
authors.forename: Fabio
authors.initials: F
authors.lastname: Bagnoli
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gambellini
authors.forename: Giuliano
authors.initials: G
authors.lastname: Bensi
authors.forename: Marirosa
authors.initials: M
authors.lastname: Mora
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Edwards
authors.forename: James M
authors.initials: JM
authors.lastname: Musser
authors.forename: Edward A
authors.initials: EA
authors.lastname: Graviss
authors.forename: John L
authors.initials: JL
authors.lastname: Telford
authors.forename: Guido
authors.initials: G
authors.lastname: Grandi
authors.forename: Immaculada
authors.initials: I
authors.lastname: Margarit
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019881:Aminoacyltransferases / Q000235:genetics; D000907:Antibodies, Bacterial / Q000097:blood; D001422:Bacterial Adhesion / Q000235:genetics / Q000502:physiology*; D001426:Bacterial Proteins / Q000235:genetics; D018441:Biofilms / Q000254:growth & development*; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000235:genetics; D004847:Epithelial Cells / Q000382:microbiology; D004848:Epithelium / Q000382:microbiology; D010861:Fimbriae, Bacterial / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D017353:Gene Deletion; D005816:Genetic Complementation Test; D006801:Humans; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D010614:Pharynx / Q000166:cytology / Q000382:microbiology*; D013290:Streptococcal Infections / Q000276:immunology; D013297:Streptococcus pyogenes / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology
chemical_list: D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; C509822:sortase C; D019881:Aminoacyltransferases; D003546:Cysteine Endopeptidases