X., Lauth von Köckritz-Blickwede M. C.W., McNamara S., Myskowski A.S., Zinkernagel B., Beall P., Ghosh R.L., Gallo V., Nizet Supplementary Material for: M1 Protein Allows Group A Streptococcal Survival in Phagocyte Extracellular Traps through Cathelicidin Inhibition M1 protein contributes to Group A <i>Streptococcus</i> (GAS) systemic virulence by interfering with phagocytosis and through proinflammatory activities when released from the cell surface. Here we identify a novel role of M1 protein in the stimulation of neutrophil and mast cell extracellular trap formation, yet also subsequent survival of the pathogen within these DNA-based innate defense structures. Targeted mutagenesis and heterologous expression studies demonstrate M1 protein promotes resistance to the human cathelicidin antimicrobial peptide LL-37, an important effector of bacterial killing within such phagocyte extracellular traps. Studies with purified recombinant protein fragments mapped the inhibition of cathelicidin killing to the M1 hypervariable N-terminal domain. A survey of GAS clinical isolates found that strains from patients with necrotizing fasciitis or toxic shock syndrome were significantly more likely to be resistant to cathelicidin than GAS M types not associated with invasive disease; M1 isolates were uniformly resistant. We conclude increased resistance to host cathelicidin and killing within phagocyte extracellular traps contribute to the propensity of M1 GAS strains to produce invasive infections. Group A Streptococcus;Streptococcus pyogenes;Virulence factor;Innate immunity;M protein;Neutrophil;Mast cell;Extracellular traps;Antimicrobial peptide;Cathelicidin 2009-02-20
    https://karger.figshare.com/articles/dataset/Supplementary_Material_for_M1_Protein_Allows_Group_A_Streptococcal_Survival_in_Phagocyte_Extracellular_Traps_through_Cathelicidin_Inhibition/5120620
10.6084/m9.figshare.5120620.v1