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J Innate Immun. 2009;1(3):202-14. doi: 10.1159/000203645. Epub 2009 Feb 20.

M1 protein allows Group A streptococcal survival in phagocyte extracellular traps through cathelicidin inhibition.

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  • 1Department of Pediatrics, University of California San Diego, La Jolla, Calif. 92093-0687, USA.

Abstract

M1 protein contributes to Group A Streptococcus (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.

PMID:
20375578
PMCID:
PMC3241932
DOI:
10.1159/000203645
[PubMed - indexed for MEDLINE]
Free PMC Article

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