title: Collagen-binding microbial surface components recognizing adhesive matrix molecule (MSCRAMM) of Gram-positive bacteria inhibit complement activation via the classical pathway.
abstract: Members of a family of collagen-binding microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) from Gram-positive bacteria are established virulence factors in several infectious diseases models. Here, we report that these adhesins also can bind C1q and act as inhibitors of the classical complement pathway. Molecular analyses of Cna from Staphylococcus aureus suggested that this prototype MSCRAMM bound to the collagenous domain of C1q and interfered with the interactions of C1r with C1q. As a result, C1r2C1s2 was displaced from C1q, and the C1 complex was deactivated. This novel function of the Cna-like MSCRAMMs represents a potential immune evasion strategy that could be used by numerous Gram-positive pathogens.
authors.affiliation: Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas 77030, USA.
authors.forename: Mingsong
authors.initials: M
authors.lastname: Kang
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Ko
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Liang
authors.forename: Caná L
authors.initials: CL
authors.lastname: Ross
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Murray
authors.forename: Magnus
authors.initials: M
authors.lastname: Höök
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D001667:Binding, Competitive / Q000276:immunology; D003094:Collagen / Q000276:immunology / Q000378:metabolism; D003167:Complement Activation / Q000276:immunology*; D015922:Complement C1q / Q000276:immunology / Q000378:metabolism; D015923:Complement C1r / Q000276:immunology / Q000378:metabolism; D003171:Complement Pathway, Classical / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006094:Gram-Positive Bacteria / Q000276:immunology* / Q000378:metabolism; D049671:History, 18th Century; D006801:Humans; D015151:Immunoblotting; D007700:Kinetics; D008958:Models, Molecular; D011485:Protein Binding / Q000276:immunology; D017434:Protein Structure, Tertiary; D020349:Surface Plasmon Resonance
chemical_list: D018829:Adhesins, Bacterial; C509820:MSCRAMM proteins, Staphylococcus; C048165:adhesin, Staphylococcus aureus; D015922:Complement C1q; D003094:Collagen; D015923:Complement C1r
keywords: C1q; Classical Complement Pathway; Collagen; Collagen-binding Proteins; Complement System; Host-Pathogen Interactions; MSCRAMM; Microbial Pathogenesis; Staphylococcus