Streptococcus pneumoniae binds collagens and C1q via the SSURE repeats of the PfbB adhesin

Abstract

The binding of Streptococcus pneumoniae to collagen is likely an important step in the pathogenesis of pneumococcal infections, but little is known of the underlying molecular mechanisms. Streptococcal surface repeats (SSURE) are highly conserved protein domains present in cell wall adhesins from different Streptococcus species. We find here that SSURE repeats of the pneumococcal adhesin plasminogen and fibronectin binding protein B (PfbB) bind to various types of collagen. Moreover, deletion of the pfbB gene resulted in a significant impairment of the ability of encapsulated or unencapsulated pneumococci to bind collagen. Notably, a PfbB SSURE domain is also bound to the complement component C1q that bears a collagen‐like domain and promotes adherence of pneumococci to host cells by acting as a bridge between bacteria and epithelial cells. Accordingly, deletion of PfbB or pre‐treatment with anti‐SSURE antibodies markedly decreased pneumococcal binding to C1q as well as C1q‐dependent adherence to epithelial and endothelial cells. Further data indicated that C1q promotes pneumococcal adherence by binding to integrin α2β1. In conclusion, our results indicate that the SSURE domains of the PfbB protein promote interactions of pneumococci with various types of collagen and with C1q. These repeats may be useful targets in strategies to control S. pneumoniae infections.

Characterization of Collagen Binding Activity of Clostridium perfringens Strains Isolated from Broiler Chickens

“…Further investigations may be warranted to better define the complex association among growth rate, toxin productions, genotypes, and pathogenicity. The collagen adhesin-like proteins, as an important virulence factor also developed by many other pathogenic Gram-positive bacteria to promote bacteria–host interaction [ 32 , 33 ], may be useful targets utilized to control multiple bacterial infections at the critical steps of initiation and persistence.…”

Engagement of α3β1 and α2β1 integrins by hypervirulent Streptococcus agalactiae in invasion of polarized enterocytes

“…Rabbit polyclonal anti-GBS serum has been previously described (De Gaetano et al, 2021 ). Rabbit anti-α 3 polyclonal (21992-1-AP, Proteintech), mouse anti-α 2 monoclonal (14-0498-80, Invitrogen), rabbit anti-β 1 polyclonal (12594-1-AP, Proteintech) and mouse anti-integrin α 5 β 1 monoclonal (MAB1969, Millipore) antibodies were obtained commercially, while rabbit anti-α 5 , -α 1 , -α V , and -β 3 polyclonal antibodies were a generous gift from Dr. G. Tarone (University of Turin, Italy) and have been previously described (Pietrocola et al, 2015 ; De Gaetano et al, 2022 ). For immunofluorescence analysis, Alexa Fluor 488-conjugated anti-rabbit IgG (ab15007) and anti-mouse FITC secondary (ab6785) antibodies, both from Abcam, were used.…”

“…Several pathogens use integrins and integrin-dependent intracellular signaling for their adhesion to and invasion of host cells (Scibelli et al, 2007 ; De Gaetano et al, 2022 ). In this process, pathogens can directly interact with integrins or use other host molecules, such as ECM components, as a bridge.…”

Antimicrobial Resistance: Two-Component Regulatory Systems and Multidrug Efflux Pumps

“…However, it can become pathogenic and reach distant sites in the host, causing several types of infections such as otitis media, sinusitis, meningitis, community-acquired pneumonia, and septicemia [ 318 ]. The switch from a harmless commensal to a pathogen depends on pneumococcal dynamic interactions with the host, including the ability to evade immune responses [ 319 , 320 , 321 , 322 , 323 , 324 ]. All these pathogenic features are associated with the capacity of modulating the expression of virulence genes that are often under the control of numerous TCS [ 325 ].…”