Role of extracellular GAPDH in Streptococcus pyogenes virulence

Abstract

Pathogens generate molecules, or virulence factors, that enable them to colonize host tissues through several mechanisms, including adhesion to host tissues, or superior invasive capability. Some allow the pathogen to evade the host's immune system. Many of these molecules are proteins that are exported to the cell's surface or secreted. Curiously, GAPDH, which is a glycolytic enzyme, is also a virulence factor that has been shown to contribute to Streptococcus pyogenes pathogenicity by each of these mechanisms.

Figure 1. Morphology of Streptococcus pyogenes

The cells are spherical, asymmetrical, and exhibit polarity. Parallel dashed lines represent the equatorial axes of the cells. The direction of growth is indicated by the diagonal arrow and cell division takes place along a single plane. During cell division, the cells remain attached, resulting in chains of cells. GAPDH is concentrated at the polar regions of the cells along the growth axis likely contributing to the polarization of the cell.

Figure 2. Cell surface structure of Streptococcus pyogenes

The peptidoglycan cell wall (shown as a arc) surrounds the plasma membrane (shown as the innermost arc). The hyaluronic acid-containing capsule (shown as the outermost arc) covers the cell wall with a gel-like coat. The peptidoglycan layer typically consists of repeating units of N-acetylglucosamine and N-acetylmuramic acid via 1,4 β-glycosidic linkages. Group A polysaccharide antigen contains N-acetylglucosamine and rhamnose. GAPDH binds to the M-protein attached to the pili (shown by the arrow).