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Group A Streptococcus Streptococcal Collagen‐like Protein (Scl‐1) Enhances Bacterial Resistance to Neutrophil Serine Proteases
Author(s) -
Kim Jessica,
Etesami Neelou,
Dohrmann Simon,
Nizet Victor,
Okumura Cheryl
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.925.11
Subject(s) - proteases , streptococcus pyogenes , cathepsin g , microbiology and biotechnology , neutrophil extracellular traps , azurophilic granule , elastase , peptidoglycan , innate immune system , antimicrobial peptides , neutrophil elastase , proteinase 3 , extracellular , biology , chemistry , myeloperoxidase , enzyme , bacteria , immune system , antimicrobial , biochemistry , immunology , inflammation , genetics , staphylococcus aureus
The streptococcal collagen‐like protein (Scl‐1) of the gram‐positive Group A Streptococcus (GAS) is thought to contribute to bacterial resistance to the killing mechanisms of cells of the innate immune system. Our previous work has shown that the Scl‐1 protein was found to enhance bacterial survival in the presence of phagocytic cells to allow persistence at the site of infection. Specifically, Scl‐1 prevented bacterial killing by preventing binding of the antimicrobial peptide LL‐37, which is a contributor to the bactericidal activity of neutrophil extracellular traps (NETs). In addition to the role of LL‐37 in extracellular killing, LL‐37 is deployed intracellularly in neutrophils along with neutrophil serine proteases found in azurophilic and specific granules. In our current study, we examine the protective effects of Scl‐1 when bacteria are intracellular, such as when they are phagocytosed by neutrophils and macrophages. A mutant strain of GAS lacking the Scl‐1 gene (ΔScl‐1) exhibited significantly decreased survival in vitro with the neutrophil serine proteases cathepsin G, elastase and lysozyme compared to wild‐type and plasmid‐complemented strains. In addition to the direct antimicrobial activity of these enzymes, the results suggest that in the context of a cell, digestion of surface molecules by these enzymes may subsequently render the bacterial more susceptible to LL‐37. Scl‐1 would thus serve as a molecular “shield” when other cell wall components are not present. We are currently investigating the synergy between the granular enzymes and LL‐37. The results suggest that Scl‐1 is critical in suppressing the effects of LL‐37 both intracellularly and extracellularly, prolonging the survival of GAS in the face of the innate immune defense system.