Journal
JOURNAL OF INNATE IMMUNITY
Volume 2, Issue 6, Pages 587-595Publisher
KARGER
DOI: 10.1159/000317672
Keywords
Antimicrobial peptides; Complement system; Innate immunity; Streptococcus; Virulence factors; Cathelicidin
Categories
Funding
- National Institutes of Health [AI77780, AI48176]
- UCSD
- NIH/NIGMS [T32 GM008666]
- EMBO Postdoctoral Fellowship
- Netherlands Organization of Scientific Research
- National Health and Medical Research Council of Australia [514639]
- Department of Employment Science and Technology (Australia) [CG001105]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R21AI048176, R01AI077780] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM008666] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Streptococcal inhibitor of complement (SIC) is a highly polymorphic extracellular protein and putative virulence factor secreted by M1 and M57 strains of group A Streptococcus (GAS). The sic gene is highly upregulated in invasive M1T1 GAS isolates following selection of mutations in the covR/S regulatory locus in vivo. Previous work has shown that SIC (allelic form 1.01) binds to and inactivates complement C5b67 and human cathelicidin LL-37. We examined the contribution of SIC to innate immune resistance phenotypes of GAS in the intact organism, using (1) targeted deletion of sic in wild-type and animal-passaged (covS mutant) M1T1 GAS harboring the sic 1.84 allele and (2) heterologous expression of sic in M49 GAS, which does not possess the sic gene in its genome. We find that M1T1 SIC production is strongly upregulated upon covS mutation but that the sic gene is not required for generation and selection of covS mutants in vivo. SIC 1.84 bound both human and murine cathelicidins and was necessary and sufficient to promote covS mutant M1T1 GAS resistance to LL-37, growth in human whole blood and virulence in a murine model of systemic infection. Finally, the sic knockout mutant M1T1 GAS strain was deficient in growth in human serum and intracellular macrophage survival. We conclude that SIC contributes to MITI GAS immune resistance and virulence phenotypes. Copyright (C) 2010 S. Karger AG, Basel
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available