Streptococcal Collagen-like Protein 1 Binds Wound Fibronectin: Implications in Pathogen Targeting.

Abstract

Group A Streptococcus (GAS) infections are responsible for significant morbidity and mortality worldwide. The outlook for an effective global vaccine is reduced because of significant antigenic variation among GAS strains worldwide. Other challenges in GAS therapy include the lack of common access to antibiotics in developing countries, as well as allergy to and treatment failures with penicillin and increasing erythromycin resistance in the industrialized world. At the portal of entry, GAS binds to newly deposited extracellular matrix, which is rich in cellular fibronectin isoforms with extra domain A (EDA, also termed EIIIA) via the surface adhesin, the streptococcal collagen-like protein 1 (Scl1). Recombinant Scl1 constructs, derived from diverse GAS strains, bind the EDA loop segment situated between the C and C' β-strands. Despite the sequence diversity in Scl1 proteins, multiple sequence alignments and secondary structure predictions of Scl1 variants, as well as crystallography and homology modeling studies, point to a conserved mechanism of Scl1-EDA binding. We propose that targeting this interaction may prevent the progression of infection. A synthetic cyclic peptide, derived from the EDA C-C' loop, binds to recombinant Scl1 with a micromolar dissociation constant. This review highlights the current concept of EDA binding to Scl1 and provides incentives to exploit this binding to treat GAS infections and wound colonization.

• Authors: Dudley H McNitt, Livingston Van De Water, Daniela Marasco, Rita Berisio, Slawomir Lukomski
• Journal: Current medicinal chemistry (Curr Med Chem) Vol. 26 Issue 11 Pg. 1933-1945 ( 2019) ISSN: 1875-533X [Electronic] United Arab Emirates
• PMID: 30182848 (Publication Type: Journal Article, Review)
• Copyright: Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Chemical References

• Antibodies
• Bacterial Proteins
• Fibronectins
• Scl1 protein, Streptococcus
• Collagen

Topics

• Antibodies (immunology)
• Bacterial Proteins (genetics, immunology, metabolism)
• Collagen (genetics, immunology, metabolism)
• Fibronectins (chemistry, immunology, metabolism)
• Humans
• Protein Binding (immunology)
• Protein Domains
• Streptococcal Infections (drug therapy, metabolism, therapy)
• Streptococcus pyogenes (chemistry, genetics)
• Wounds and Injuries (microbiology)