Pili mediate specific adhesion of Streptococcus pyogenes to human tonsil and skin

Abstract

SummaryVery little is known about the biological functions of pili that have recently been found to be expressed by important Gram-positive pathogens such as Corynebacterium diphtheriae, Streptococcus agalacticae, S. pneumoniae and S. pyogenes. Using various ex vivo tissue and cellular models, here we show that pili mediate adhesion of serotype M1 S. pyogenes strain SF370 to both human tonsil epithelium and primary human keratinocytes, which represent the two main sites of infection by this human-specific pathogen. Mutants lacking minor pilus subunits retained the ability to express cell-surface pili, but these were functionally defective. In contrast to above, pili were not required for S. pyogenes adhesion to either immortalized HEp-2 or A549 cells, highlighting an important limitation of these extensively used adhesion/invasion models. Adhering bacteria were internalized very effectively by both HEp-2 and A549 cells, but not by tonsil epithelium or primary keratinocytes. While pili acted as the primary adhesin, the surface M1 protein clearly enhanced adhesion to tonsil, but surprisingly, had the opposite effect on adhesion to keratinocytes. These studies provide clear evidence that S. pyogenes pili display an adhesive specificity for clinically relevant human tissues and are likely to play a critical role in the initial stages of infection.

The Extracellular Protein Factor Epf from Streptococcus pyogenes Is a Cell Surface Adhesin That Binds to Cells through an N-terminal Domain Containing a Carbohydrate-binding Module

“…Group A streptococci are known to produce a plethora of adhesins, which vary among different serotypes. Examples include the M-protein, which is the major cell wall-associated virulence factor (2), adhesive pili that are assembled by the action of sortase enzymes (44), and the fibronectin-binding protein FbaB (40). These are all anchored covalently to the cell wall by the action of sortases that recognize a characteristic LPXTG sorting motif.…”

Streptococcus pyogenes M49 Plasminogen/Plasmin Binding Facilitates Keratinocyte Invasion via Integrin-Integrin-linked Kinase (ILK) Pathways and Protects from Macrophage Killing

“…The capsule itself has been shown to interact directly with CD44 (55), thereby allowing paracellular transmigration (56). Moreover, fibronectin-binding protein SfbI and the GAS pilus have been described to be involved in keratinocyte adherence (50,51,57). However, conflicting data exist and most likely these interactions are not universal but rather serotype dependent (58,59).…”

“…First, epithelial cells of the human larynxs and pharynxs have been extensively studied for plasminogen/ plasmin-mediated adherence and internalization mechanisms (22,33,50,51). Although it has been shown that GAS use paracellular transmigration through pharyngeal host cell monolayers (33), nothing is known about cell surface receptors binding to GAS surface-bound plasminogen/plasmin and the intracellular pathways exploited by the bacteria.…”

Human pathogenic streptococcal proteomics and vaccine development

“…The identification of pili in streptococcal species has only been recently published [98-100]. Pili of S. pyogenes serotype M1 promote adhesion to human tonsil epithelium and primary human keratinocytes and the formation of biofilm [101,102], while the pili proteins of S. agalactiae facilitate adherence and invasion of brain endothelium [103]. The pilus operons promoting synthesis and assembly of pili are found in genomic islands such as the FCT pathogenicity island in S. pyogenes [98], the rlrA pathogenicity island in S. pneumoniae [100,104], and in novel genomic islands in S. agalactiae [99,105].…”