A Second Pilus Type in Streptococcus pneumoniae Is Prevalent in Emerging Serotypes and Mediates Adhesion to Host Cells

Abstract

Analysis of publicly available genomes of Streptococcus pneumoniae has led to the identification of a new genomic element containing genes typical of gram-positive pilus islets (PIs). Here, we demonstrate that this genomic region, herein referred to as PI-2 (consisting of pitA, sipA, pitB, srtG1, and srtG2) codes for a second functional pilus in pneumococcus. Polymerization of the PI-2 pilus requires the backbone protein PitB as well as the sortase SrtG1 and the signal peptidase-like protein SipA. Presence of PI-2 correlates with the genotype as defined by multilocus sequence typing and clonal complex (CC). The PI-2-positive CCs are associated with serotypes 1, 2, 7F, 19A, and 19F, considered to be emerging serotypes in both industrialized and developing countries. Interestingly, strains belonging to CC271 (where sequence type 271 is the predicted founder of the CC) contain both PI-1 and PI-2, as revealed by genome analyses. In these strains both pili are surface exposed and independently assembled. Furthermore, in vitro experiments provide evidence that the pilus encoded by PI-2 of S. pneumoniae is involved in adherence. Thus, pneumococci encode at least two types of pili that play a role in the initial host cell contact to the respiratory tract and are potential antigens for inclusion in a new generation of pneumococcal vaccines.

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).…”

Polymeric Immunoglobulin Receptor-mediated Invasion of Streptococcus pneumoniae into Host Cells Requires a Coordinate Signaling of SRC Family of Protein-tyrosine Kinases, ERK, and c-Jun N-terminal Kinase

“…In addition, pneumococci produce adhesins, which interact directly with cellular receptors and consequently, these interactions promote bacterial adherence to and invasion into host cells (4,9). The major adhesin of S. pneumoniae, the pneumococcal surface protein C (PspC) 4 (also designated as CbpA or SpsA) represents a multifunctional surface-exposed cholinebinding protein and plays an important role in invasion and pathogenesis of this versatile pathogen.…”