Group A streptococcal invasion

Harry S. Courtney and Andreas Podbielski of host cells

Group A streptococci (GAS), Streptococcus pyogenes, are beta-hemolytic, Grampositive, pyogenic cocci that usually grow in chains. S. pyogenes is classified as group A based on serological reactions with its C carbohydrate, which consists of polymers of rhamnose substituted with N-acetylglucosamine (Lancefield, 1933). For epidemiological purposes, GAS are further classified into more than 100 different types based on serological reactions with the variable domains of M proteins, or, more recently, based on 5' emm gene sequences (Beall et al., 1996). Other typing schemes based on serological reactions with serum opacity factor, T proteins, and R proteins are also used (Johnson and Kaplan, 1993).

S. pyogenes is almost exclusively associated with humans and commonly causes a variety of diseases, including pharyngotonsillitis, impetigo, scarlet fever, and more severe infections, such as puerperal sepsis, myositis, necro-tizing fasciitis, and toxic shock syndrome. Among several ofthe nonsuppu-rative complications ofgroup A streptococcal infections are acute rheumatic fever and acute glomerulonephritis, which are usually preceded by infections of the throat and skin, respectively. These sequelae are thought to be due to autoimmune T- and B-cell responses induced by streptococcal products. Accumulating evidence also suggests that group A streptococcal infections may lead to other autoimmune diseases, such as obsessive compulsive disorders, or they may exacerbate others such as guttate psoriasis (reviewed by Cunningham, 2000).


To establish these infections, the streptococcus must first attach to the epithelium of the host. This attachment is accomplished by specific interactions

  • Figure 8.1. An electron micrograph of streptococcal adhesion to a human buccal
  • epithelial cell.

<3 between surface structures of the streptococcus (adhesins) and receptors on

  • host cells (reviewed by Courtney et al., 2002). Attachment of streptococci to
  • a human buccal epithelial cell is shown in Fig. 8.1. Note that the epithelial s cell has a ruffled surface that is due to convoluted ridges that cover its sur face and that appear as projections in electron micrographs of thin sections. Similar ridges are found on the surfaces of human pharyngeal and tonsillar epithelial cells (Stenfors et al., 2000). Streptococcal attachment to these cells occurs primarily by interactions with receptors on these ridges, and adhesion is often mediated by multiple interactions resulting in high-avidity binding.

Early adhesion experiments demonstrated that streptococci did not attach to all buccal cells but instead attached primarily to those cells coated with fibronectin (Abraham et al., 1983; Simpson and Beachey, 1983). These findings coupled with additional research confirmed that fibronectin was a receptor for GAS (Courtney et al., 1986). Lipoteichoic acid (LTA) was the first streptococcal adhesin to be identified that reacted with fibronectin (Beachey and Ofek, 1976; Courtney et al., 1986). Subsequently, at least 24 other adhesins have been described, many of which react with fibronectin or other

Table 8.1. Putative streptococcal adhesins-invasins and receptors

Adhesin-Invasin Receptor


C5a peptidase


Collagen-binding protein Fba(FbaA) FbaB FBP54

Galactose-binding protein G3PDH(or SDH)

Hyaluronic acid

Lbp Lsp

Lipoteichoic acid

M protein

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