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.

Population and Whole Genome Sequence Based Characterization of Invasive Group A Streptococci Recovered in the United States during 2015

“…This possibility is further suggested by the existence of a close R28 homolog in group B streptococci that commonly colonize the vaginal epithelium (30). The acquisition of the tee89 gene in emergent clade 3 emm89 may have conferred new functional adherence or immune evasion properties (3,36,41). The recent increased superantigen complement in emm1 subclones described in China is reason for increased awareness of the enhanced virulence potential imposed by already impactful iGAS strains, wherein emm12 strains facilitated the horizontal transfer of scarlet fever-associated mobile elements carrying speC and ssa to the emm1/ST28 lineage (33).…”

Science‐in‐brief: Streptococcus zooepidemicus: a versatile opportunistic pathogen that hedges its bets in horses

“…For example, a disruptive inversion of the FimIV locus, which encodes a putative pilus in many strains of S. zooepidemicus [5], was shown to be mediated by PinR [32]. Hair-like pilus structures on the surface of streptococci can play important roles in the adhesion and survival of streptococci [36,37], but can also be targeted as components of subunit vaccines [29]. Therefore, the reversible regulation of FimIV could assist S. zooepidemicus to successfully fulfil its opportunistic lifestyle.…”

Incremental Contributions of FbaA and Other Impetigo-Associated Surface Proteins to Fitness and Virulence of a Classical Group A Streptococcal Skin Strain

“…Other studies have reported that the GAS pilus alters the susceptibility of GAS to phagocytosis in whole human blood by either increased bacterial killing (M1T1 strain; FCT-2, emm pattern A-C) or decreased bacterial killing (M2T2 strain; FCT-6, emm pattern E) (33,34). The emm pattern D strain Alab49 expresses the FCT-3 form of pili (T serotype T3/13/B) (7).…”