RrgA is a pilus‐associated adhesin in Streptococcus pneumoniae

Abstract

SummaryAdherence to host cells is important in microbial colonization of a mucosal surface, and Streptococcus pneumoniae adherence was significantly enhanced by expression of an extracellular pilus composed of three subunits, RrgA, RrgB and RrgC. We sought to determine which subunit(s) confers adherence. Bacteria deficient in RrgA are significantly less adherent than wild-type organisms, while overexpression of RrgA enhances adherence. Recombinant monomeric RrgA binds to respiratory cells, as does RrgC with less affinity, and pre-incubation of epithelial cells with RrgA reduces adherence of wild-type piliated pneumococci. Non-adherent RrgA-negative, RrgBand RrgC-positive organisms produce pili, suggesting that pilus-mediated adherence is due to expression of RrgA, rather than the pilus backbone itself. In contrast, RrgA-positive strains with disrupted rrgB and rrgC genes exhibit wild-type adherence despite failure to produce pili by Western blot or immunoelectron microscopy. The density of bacteria colonizing the upper respiratory tract of mice inoculated with piliated RrgA-negative pneumococci was significantly less compared with wild-type; in contrast, non-piliated pneumococci expressing non-polymeric RrgA had similar numbers of bacteria in the nasopharynx as piliated wild-type bacteria. These data suggest that RrgA is central in pilus-mediated adherence and disease, even in the absence of polymeric pilus production.

Temporal upregulation of host surface receptors provides a window of opportunity for bacterial adhesion and disease

“…This interaction in turn stimulates multiple signal transduction pathways including phospholipase C, D, A2, mitogen-activated protein kinases (MAPKs) and the phosphatidylinositol-calcium second messenger system, thereby increasing the expression of pneumococcal adhesion receptors pIgR or PECAM-1 [64][65][66]. In addition, pneumococcal pilus-1 adhesin RrgA and pilus-2 adhesin PitB have been implicated in pneumococci-mediated adhesion and invasion of brain endothelial cells and respiratory epithelial cells [67][68][69].…”

Toll-like Receptor (TLR) 2 Mediates Inflammatory Responses to Oligomerized RrgA Pneumococcal Pilus Type 1 Protein

“…The structural proteins of the pneumococcal pilus type 1 are among the most recent ones to be investigated (13)(14)(15)(16). The type 1 pilus was shown to act as an adhesin (17,18), enhance colonization in a mouse model (19), and facilitate the formation of microcolonies and biofilms (20). Piliated pneumococcal strains induce significantly more TNF-␣ in a mouse model of intraperitoneal sepsis than pilus-negative isogenic controls (19).…”

The Choline-binding Protein PspC of Streptococcus pneumoniae Interacts with the C-terminal Heparin-binding Domain of Vitronectin

“…Adhesive properties are known for a number of pneumococcal surface proteins recognizing plasmin(ogen), fibronectin, thrombospondin-1, and vitronectin (8 -17). A subpopulation of pneumococci produces pili, encoded by the pilus islet (PI)-1 or PI-2, and at least the RrgA of PI-1 functions as an adhesin (17)(18)(19)(20). However, one of the most important adhesins of S. pneumoniae is the pneumococcal surface protein C (PspC, also referred to as CbpA or SpsA), which belongs to the family of pneumococcal cholinebinding proteins.…”