The pavA gene of Streptococcus pneumoniae encodes a fibronectin‐binding protein that is essential for virulence

Abstract

Streptococcus pneumoniae colonizes the nasopharynx in up to 40% of healthy subjects, and is a leading cause of middle ear infections (otitis media), meningitis and pneumonia. Pneumococci adhere to glycosidic receptors on epithelial cells and to immobilized fibronectin, but the bacterial adhesins mediating these reactions are largely uncharacterized. In this report we describe a novel pneumococcal protein PavA, which binds fibronectin and is associated with pneumococcal adhesion and virulence. The pavA gene, present in 64 independent isolates of S. pneumoniae tested, encodes a 551 amino acid residue polypeptide with 67% identical amino acid sequence to Fbp54 protein in Streptococcus pyogenes. PavA localized to the pneumococcal cell outer surface, as demonstrated by immunoelectron microscopy, despite lack of conventional secretory or cell‐surface anchorage signals within the primary sequence. Full‐length recombinant PavA polypeptide bound to immobilized human fibronectin in preference to fluid‐phase fibronectin, in a heparin‐sensitive interaction, and blocked binding of wild‐type pneumococcal cells to fibronectin. However, a C‐terminally truncated PavA′ polypeptide (362 aa residues) failed to bind fibronectin or block pneumococcal cell adhesion. Expression of pavA in Enterococcus faecalis JH2–2 conferred > sixfold increased cell adhesion levels to fibronectin over control JH2–2 cells. Isogenic mutants of S. pneumoniae, either abrogated in PavA expression or producing a 42 kDa C‐terminally truncated protein, showed up to 50% reduced binding to immobilized fibronectin. Inactivation of pavA had no effects on growth rate, cell morphology, cell‐surface physico‐chemical properties, production of pneumolysin, autolysin, or surface proteins PspA and PsaA. Isogenic pavA mutants of encapsulated S. pneumoniae D39 were approximately 104‐fold attenuated in virulence in the mouse sepsis model. These results provide evidence that PavA fibronectin‐binding protein plays a direct role in the pathogenesis of pneumococcal infections.

Identification and characterization of a fibronectin-binding protein from Clostridium difficile

“…Similar to the putative Fbp from B. subtilis, Fbp68 does not appear to possess a classical signal peptide (von Heijne, 1985) as do most Fbps from other bacteria (Navarre & Schneewind, 1999). Fbp68 displays the best homology (44 % identity) with the putative Fbp of B. subtilis mentioned above and 38 % and 39 % identity, respectively, with the adherence and virulence protein A (PavA) of Streptococcus pneumoniae (AAF05332) and FBP54 of Streptococcus pyogenes (AAA57236), for which a clear role in adhesion to target cells has been established (Courtney et al, 1994;Holmes et al, 2001). In addition, Fbp68 displays 66 % identity with the fibronectin-binding domain of FBP54 (Courtney et al, 1994).…”

The arsenal of virulence factors deployed byListeria monocytogenesto promote its cell infection cycle

“…FbpA displays a strong homology to atypical fibronectin-binding proteins, such as Streptococcus pneumoniae PavA, 43 S. pyogenes Fbp54, 44 and S. gordonii FbpA. 45 FbpA is exposed at the surface of the bacteria despite lacking a canonical signal peptide, as its streptococcal homologs.…”

Inactivation of a gene for a fibronectin-binding protein of the oral bacterium Streptococcus mutans partially impairs its adherence to fibronectin

“…When the translated sequence of the S. mutans fibronectin-binding protein was compared to the fibronectin-binding protein of S. gordonii (FbpA), the alignment showed that 409 of 549 (74%) amino acids were identical and 70 were conserved substitutions indicating an overall similarity of 87% [10]. Similar levels of identity were found for the fibronectin-binding PavA protein of S. pneumoniae and the putative fibronectin binding protein of the oral streptococcus, Streptococcus sanguinis [19,20]. Fig.…”

“…Also, several species of streptococci express atypical fibronectin-binding proteins that do not contain a secretion signal, anchoring motif, or repeat sequences for binding to fibronectin. These atypical fibronectin-binding proteins include FBP54 of S. pyogenes, PavA of S. pneumoniae, and FbpA of S. gordonii [7,10,19]. Chia et al observed that S. mutans cells could adsorb on their surface soluble fibronectin present in plasma [14].…”