Group A Streptococcus produce pilus-like structures containing protective antigens and Lancefield T antigens

Abstract

Although pili have long been recognized in Gram-negative pathogens as important virulence factors involved in adhesion and invasion, very little is known about extended surface organelles in Gram-positive pathogens. Here we report that Group A Streptococcus (GAS), a Gram-positive human-specific pathogen that causes pharyngitis, impetigo, invasive disease, necrotizing fasciitis, and autoimmune sequelae has long, surface-exposed, pilus-like structures composed of members of a family of extracellular matrix-binding proteins. We describe four variant pili and show that each is recognized by a specific serum of the Lancefield T-typing system, which has been used for over five decades to characterize GAS isolates. Furthermore, we show that immunization of mice with a combination of recombinant pilus proteins confers protection against mucosal challenge with virulent GAS bacteria. The data indicate that induction of a protective immune response against these structures may be a useful strategy for development of a vaccine against disease caused by GAS infection.fibronectin-binding ͉ Gram-positive

Intramolecular Isopeptide Bonds Give Thermodynamic and Proteolytic Stability to the Major Pilin Protein of Streptococcus pyogenes

“…These pili, which are extremely thin (2-5 nm in diameter) but can extend up to 4 m from the bacterial cell surface (4), are formed as covalently linked polymers through the action of cysteine transpeptidase enzymes called sortases. In this process, which is common to a number of Gram-positive bacterial pathogens, the pilus backbone is formed from a single protein subunit, the so-called major pilin, by the covalent, endto-end polymerization of major pilin subunits, generating an assembly resembling beads on a string (5)(6)(7).…”

Hyperthin nanochains composed of self-polymerizing protein shackles

“…Pili, long filamentous protein structures that extend from bacterial surfaces 24 , form by covalent polymerization of subunits catalysed by an enzyme called sortase [25][26][27] . As pilus subunits are arranged head-to-tail, pili are thin (2-5 nm).…”

High throughput genomic and proteomic technologies in the fight against infectious diseases

“…Interestingly, three of these proteins were found to assemble into pili. Based on these pioneering findings, a search for molecular signatures for typical pilus regions was also applied by Mora et al [64] in a comparative reverse vaccinology study aimed to identify S. pyogenes vaccine candidates. Genome sequence analysis of five different circulating strains suggested that a multicomponent vaccine combining 12 backbone variants of pilus protein genes might provide protection against over 90% of circulating strains of S. pyogenes.…”