Structural Insights into Serine-rich Fimbriae from Gram-positive Bacteria

Abstract

The serine-rich repeat family of fimbriae play important roles in the pathogenesis of streptococci and staphylococci. Despite recent attention, their finer structural details and precise adhesion mechanisms have yet to be determined. Fap1 (Fimbriae-associated protein 1) is the major structural subunit of serine-rich repeat fimbriae from Streptococcus parasanguinis and plays an essential role in fimbrial biogenesis, adhesion, and the early stages of dental plaque formation. Combining multidisciplinary, high resolution structural studies with biological assays, we provide new structural insight into adhesion by Fap1. We propose a model in which the serine-rich repeats of Fap1 subunits form an extended structure that projects the N-terminal globular domains away from the bacterial surface for adhesion to the salivary pellicle. We also uncover a novel pH-dependent conformational change that modulates adhesion and likely plays a role in survival in acidic environments.

New Cell Surface Protein Involved in Biofilm Formation by Streptococcus parasanguinis

“…Electron microscopy (EM) studies were conducted to detect the presence of peritrichous fimbriae and short fibrils on the bacterial cell surface. Wild-type, bapA1, fap1 single-mutant, and bapA1 fap1 doublemutant cells were prepared and treated as described by Ramboarina et al (37). Briefly, samples were diluted in PBS (100 mM phosphate buffer, pH 7.4, 150 mM NaCl) to the appropriate concentration for electron microscopy studies.…”

“…The Fap1 polypeptide, on the other hand, functions as an adhesin to initiate bacterial attachment, and the glycans attached to Fap1 mediate the later steps of biofilm development (46). Although a Fap1-like protein from Streptococcus pneumoniae has been implicated in cell-cell interactions (39), Fap1 does not appear to be involved in this type of interaction, since it does not form dimers under physiological conditions (37). Furthermore, the N-terminal region of BapA1 was determined to mediate the BapA1-BapA1 interaction.…”

Platelet-Bacterial Interactions as Therapeutic Targets in Infective Endocarditis

“…The platelet receptor that SraP binds to is not currently known. SraP shares similarility with a group of cell wall-associated glycoproteins (Ramboarina et al, 2010) found in a number of other organisms including Streptococcus sanguinis (Plummer et al, 2005), Streptococcus gordonii both of which have been have been shown to bind to platelet GPIbα. Interestingly however, SraP does not seem to bind to GPIbα.…”

Stick to Your Gums

“…Both proteins mediate adhesion to salivary pellicle through recognition of sialic-acid-containing components, including salivary mucin MG2 and salivary agglutinin (Takamatsu et al, 2006). Discrete domains have been identified within these Srr proteins for mediating initial pellicle attachment vs. biofilm development (Wu et al, 1998(Wu et al, , 2007Takamatsu et al, 2006;Ramboarina et al, 2010), indicating the capacity of these adhesins to perform multiple adhesive functions simultaneously.…”

“…High-resolution studies with Streptococcus parasanguinis Srr protein Fap1 (Ramboarina et al, 2010) suggest that the dipeptide S(V/I/E) repeats within the C-terminal region form a superhelical extended stalk that projects the N-terminal protein domain away from the bacterial cell surface. Each protein molecule is approximately 300 nm in length, and it is hypothesized that the molecules might be cross-linked head to tail via N-terminal lysine residues to generate 600 nm or longer fibrils.…”