<i>Streptococcus pneumoniae</i> binds collagens and C1q via the <scp>SSURE</scp> repeats of the <scp>PfbB</scp> adhesin

Gaetano, Giuseppe Valerio De; Coppolino, Francesco; Lentini, Germana; Famà, Agata; Cullotta, Chiara; Raffaele, Ivana; Motta, Chiara; Teti, Giuseppe; Speziale, Pietro; Pietrocola, Giampiero; Beninati, Concetta

doi:10.1111/mmi.14920

Cited by 5 publications

(1 citation statement)

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“…C1q binds to discoidal domain receptor 2 (DDR2) to regulate metalloproteinase expression for wound healing due to its specific collagen-like structure ( 23 ). The structure of the C1q collagen region binds to the sequence of fibronectin-binding protein B (PfbB) on the surface of Streptococcus pneumoniae and promotes the adhesion of Streptococcus pneumoniae to host cells and participates in the process of pneumococcal infection ( 24 ). Complement activation is well documented in the progression of autoimmune diseases and is especially important in the development, diagnosis and prognostic monitoring of lupus nephritis ( 25 , 26 ).…”

Section: Introductionmentioning

confidence: 99%

C1q and central nervous system disorders

2023

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C1q is a crucial component of the complement system, which is activated through the classical pathway to perform non-specific immune functions, serving as the first line of defense against pathogens. C1q can also bind to specific receptors to carry out immune and other functions, playing a vital role in maintaining immune homeostasis and normal physiological functions. In the developing central nervous system (CNS), C1q functions in synapse formation and pruning, serving as a key player in the development and homeostasis of neuronal networks in the CNS. C1q has a close relationship with microglia and astrocytes, and under their influence, C1q may contribute to the development of CNS disorders. Furthermore, C1q can also have independent effects on neurological disorders, producing either beneficial or detrimental outcomes. Most of the evidence for these functions comes from animal models, with some also from human specimen studies. C1q is now emerging as a promising target for the treatment of a variety of diseases, and clinical trials are already underway for CNS disorders. This article highlights the role of C1q in CNS diseases, offering new directions for the diagnosis and treatment of these conditions.

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Section: Introductionmentioning

confidence: 99%

C1q and central nervous system disorders

2023

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

Gaetano

Coppolino

Lentini

et al. 2022

Molecular Microbiology

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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.

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

De Gaetano,

Lentini,

Coppolino

et al. 2024

Front. Microbiol.

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The gut represents an important site of colonization of the commensal bacterium Streptococcus agalactiae (group B Streptococcus or GBS), which can also behave as a deadly pathogen in neonates and adults. Invasion of the intestinal epithelial barrier is likely a crucial step in the pathogenesis of neonatal infections caused by GBS belonging to clonal complex 17 (CC17). We have previously shown that the prototypical CC17 BM110 strain invades polarized enterocyte-like cells through their lateral surfaces using an endocytic pathway. By analyzing the cellular distribution of putative GBS receptors in human enterocyte-like Caco-2 cells, we find here that the alpha 3 (α3) and alpha 2 (α2) integrin subunits are selectively expressed on lateral enterocyte surfaces at equatorial and parabasal levels along the vertical axis of polarized cells, in an area corresponding to GBS entry sites. The α3β1 and α2β1 integrins were not readily accessible in fully differentiated Caco-2 monolayers but could be exposed to specific antibodies after weakening of intercellular junctions in calcium-free media. Under these conditions, anti-α3β1 and anti-α2β1 antibodies significantly reduced GBS adhesion to and invasion of enterocytes. After endocytosis, α3β1 and α2β1 integrins localized to areas of actin remodeling around GBS containing vacuoles. Taken together, these data indicate that GBS can invade enterocytes by binding to α3β1 and α2β1 integrins on the lateral membrane of polarized enterocytes, resulting in cytoskeletal remodeling and bacterial internalization. Blocking integrins might represent a viable strategy to prevent GBS invasion of gut epithelial tissues.

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

Cited by 5 publications

References 95 publications

C1q and central nervous system disorders

C1q and central nervous system disorders

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

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

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