PavB is a surface‐exposed adhesin of Streptococcus pneumoniae contributing to nasopharyngeal colonization and airways infections

Abstract

SummaryThe genomic analysis of Streptococcus pneumoniae strains identified the Pneumococcal adherence and virulence factor B (PavB), whose repetitive sequences, designated Streptococcal Surface REpeats (SSURE), interact with human fibronectin. Here, we showed the gene in all tested pneumococci and identified that the observed differences in the molecular mass of PavB rely on the number of repeats, ranging from five to nine SSURE. PavB interacted with fibronectin and plasminogen in a dosedependent manner as shown by using various SSURE peptides. In addition, we identified PavB as colonization factor. Mice infected intranasally with DpavB pneumococci showed significantly increased survival times compared with wild-type bacteria. Importantly, the pavB-mutant showed a delay in transmigration to the lungs as observed in real-time using bioluminescent pneumococci and decreased colonization rates in a nasopharyngeal carriage model. In co-infection experiments the wild-type outcompeted the pavB-mutant and infections of epithelial cells demonstrated that PavB contributes to adherence to host cell. Blocking experiments suggested a function of PavB as adhesin, which was confirmed by direct binding of SSURE peptides to host cells. Finally, PavB may represent a new vaccine candidate as SSURE peptides reacted with human sera. Taken together, PavB is a surface-exposed adhesin, which contributes to pneumococcal colonization and infections of the respiratory airways.

Binding of Streptococcus pneumoniae Endopeptidase O (PepO) to Complement Component C1q Modulates the Complement Attack and Promotes Host Cell Adherence

“…Colonization of host cells is an important step in the pathogenesis of any infectious agents including pneumococci, which have developed multiple strategies such as expression of adhesins or acquirement of various host proteins to facilitate colonization (12,18,(22)(23)(24)(25)(26)(27). We have recently reported a novel mechanism of pneumococcal-host interaction whereby C1q, which is primarily involved in the initiation of the classical complement pathway, directly interacts with pneumococci and functions as a molecular bridge facilitating pneumococcal colonization of host cells (22).…”

“…Additionally, these virulence factors function as adhesins that either interact directly with the host cell surface receptors or utilize host proteins as a molecular bridge between the bacteria and the host to facilitate colonization. Host proteins include extracellular matrix and serum proteins such as fibronectin, thrombospondin, vitronectin, plasminogen, Factor H, C4BP, and C1q (12,18,(22)(23)(24)(25)(26)(27).…”

Heterologous expression of pneumococcal virulence factor PspC on the surface of Lactococcus lactis confers adhesive properties

“…Attachment of S. pneumoniae to respiratory epithelial cells is mediated by serum or extracellular matrix proteins including complement Factor H, thrombospondin-1 and vitronectin (Agarwal et al, 2010b;Bergmann et al, 2009;Hammerschmidt et al, 2007;Rennemeier et al, 2007). In addition, pneumococci produce surface proteins interacting directly with host cellular receptors such as the choline-binding protein PspC (pneumococcal surface protein C, also referred to as CbpA or SpsA), RrgA of Pilus-1, PavB and PsrP (Barocchi et al, 2006;Elm et al, 2004;Jensch et al, 2010;Orihuela et al, 2004;Zhang et al, 2000). Although the repertoire of virulence factors and adhesins differs among pneumococcal isolates, redundant virulence factors must be present in pneumococci as mutations in single genes can be compensated for by others (Bergmann & Hammerschmidt, 2006;Kadioglu et al, 2008;Nobbs et al, 2009).…”

Repeating Structures of the Major Staphylococcal Autolysin Are Essential for the Interaction with Human Thrombospondin 1 and Vitronectin

“…However, Eap also exhibits repeating sequences that are involved in binding to hTSP-1, Vn, and other extracellular matrix proteins (13). Similarly, pneumococcal proteins composed of repetitive sequences, such as the PspC and PavB proteins, interact via their repeats with Vn and fibronectin, respectively (27,66).…”