title: Role for streptococcal collagen-like protein 1 in M1T1 group A Streptococcus resistance to neutrophil extracellular traps.
abstract: Streptococcal collagen-like protein 1 (Scl-1) is one of the most highly expressed proteins in the invasive M1T1 serotype group A Streptococcus (GAS), a globally disseminated clone associated with higher risk of severe invasive infections. Previous studies using recombinant Scl-1 protein suggested a role in cell attachment and binding and inhibition of serum proteins. Here, we studied the contribution of Scl-1 to the virulence of the M1T1 clone in the physiological context of the live bacterium by generating an isogenic strain lacking the scl-1 gene. Upon subcutaneous infection in mice, wild-type bacteria induced larger lesions than the Δscl mutant. However, loss of Scl-1 did not alter bacterial adherence to or invasion of skin keratinocytes. We found instead that Scl-1 plays a critical role in GAS resistance to human and murine phagocytic cells, allowing the bacteria to persist at the site of infection. Phenotypic analyses demonstrated that Scl-1 mediates bacterial survival in neutrophil extracellular traps (NETs) and protects GAS from antimicrobial peptides found within the NETs. Additionally, Scl-1 interferes with myeloperoxidase (MPO) release, a prerequisite for NET production, thereby suppressing NET formation. We conclude that Scl-1 is a virulence determinant in the M1T1 GAS clone, allowing GAS to subvert innate immune functions that are critical in clearing bacterial infections.
authors.affiliation: Department of Pediatrics, University of California, San Diego, La Jolla, California, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Döhrmann
authors.affiliation: Department of Pediatrics, University of California, San Diego, La Jolla, California, USA.
authors.forename: Sabina
authors.initials: S
authors.lastname: Anik
authors.affiliation: Department of Pediatrics, University of California, San Diego, La Jolla, California, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Olson
authors.affiliation: Department of Pediatrics, University of California, San Diego, La Jolla, California, USA.
authors.forename: Ericka L
authors.initials: EL
authors.lastname: Anderson
authors.affiliation: Department of Biology, Occidental College, Los Angeles, California, USA.
authors.forename: Neelou
authors.initials: N
authors.lastname: Etesami
authors.affiliation: Department of Biology, Occidental College, Los Angeles, California, USA.
authors.forename: Hyewon
authors.initials: H
authors.lastname: No
authors.affiliation: Department of Biology, Occidental College, Los Angeles, California, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Snipper
authors.affiliation: Department of Pediatrics, University of California, San Diego, La Jolla, California, USA Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA vnizet@ucsd.edu okumura@oxy.edu.
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
authors.affiliation: Department of Pediatrics, University of California, San Diego, La Jolla, California, USA Department of Biology, Occidental College, Los Angeles, California, USA vnizet@ucsd.edu okumura@oxy.edu.
authors.forename: Cheryl Y M
authors.initials: CY
authors.lastname: Okumura
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D002478:Cells, Cultured; D017353:Gene Deletion; D006801:Humans; D057131:Immune Evasion; D015603:Keratinocytes / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D050296:Microbial Viability; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology*; D010586:Phagocytes / Q000276:immunology / Q000382:microbiology; D013290:Streptococcal Infections / Q000382:microbiology / Q000473:pathology; D013297:Streptococcus pyogenes / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D037521:Virulence Factors