Department of Medicine, Division of Infectious Diseases and Immunology
Biochemistry, Biophysics, and Structural Biology | Immunology and Infectious Disease | Infectious Disease
The pneumococcal type 1 pilus is an inflammatory and adherence-promoting structure associated with increased virulence in mouse models. We show that RrgA, an ancillary pilus subunit devoid of a lipidation motif, particularly when presented as part of an oligomer, is a TLR2 agonist. The surface-exposed domain III, and in particular a 49-amino acid sequence (P3), of the protein is responsible for the TLR2 activity of RrgA. A pneumococcal mutant carrying RrgA with a deletion of the P3 region was significantly reduced in its ability to activate TLR2 and induce TNF-alpha responses after mouse intraperitoneal infection, whereas no such difference could be noted when TLR2(-/-) mice were challenged, further implicating this region in recognition by TLR2. Thus, we conclude that the type 1 pneumococcal pilus can activate cells via TLR2, and the ancillary pilus subunit RrgA is a key component of this activation.
Bacterial Pathogenesis, Cell Surface Protein, Streptococcus, Toll-like Receptors (TLR), Virulence Factors
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© 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Publisher PDF posted after 12 months as allowed by the publisher's author rights policy at https://www.asbmb.org/journals-news/editorial-policies.
DOI of Published Version
J Biol Chem. 2013 Jan 25;288(4):2665-75. doi: 10.1074/jbc.M112.398875. Epub 2012 Dec 11. Link to article on publisher's site
The Journal of biological chemistry
Basset A, Zhang F, Benes C, Sayeed S, Herd M, Thompson C, Golenbock DT, Camilli A, Malley R. (2013). Toll-like receptor (TLR) 2 mediates inflammatory responses to oligomerized RrgA pneumococcal pilus type 1 protein. Infectious Diseases and Immunology Publications. https://doi.org/10.1074/jbc.M112.398875. Retrieved from https://escholarship.umassmed.edu/infdis_pp/368