10.1021/acsnano.9b02587 [PubMed] [CrossRef] [Google Scholar] Beghetto, E. , Gargano, N. , Ricci, S. , Garufi, G. , Peppoloni, S. , Montagnani, F. et al. a bridge between bacteria and epithelial cells. Accordingly, deletion of PfbB or pre\treatment with anti\SSURE antibodies markedly decreased pneumococcal binding to C1q as well as C1q\dependent adherence to epithelial and endothelial cells. Further data indicated that C1q promotes pneumococcal adherence by binding to integrin 21. In conclusion, our results indicate that this SSURE domains of the PfbB protein promote interactions of pneumococci with various types of collagen and with C1q. These repeats may be useful targets in strategies to control infections. Abstract We show here that this SSURE domains of the bacterial cell wall adhesin PfbB contribute to the ability of pneumococci to bind various types of collagens and C1q, a match component. We also show that C1q functions as a bridge between PfbB SSURE domains and the 21 integrin thereby promoting adherence to, and invasion of, endothelial and epithelial cells. Targeting SSURE domains may be advantageous in option strategies to control pneumococcal infections. 1.?INTRODUCTION (or the pneumococcus) is an Parimifasor encapsulated Gram\positive organism that is the main cause of community\acquired pneumonia and other frequent infections, such Parimifasor as otitis media and meningitis (Bogaert et al.,?2004). Although pneumococci asymptomatically colonize the upper airways, they frequently shift from a commensal to a pathogenic condition within the host. It has been estimated that almost 1 million children below 5?years of age die from, and 15 million become ill with, pneumococcal disease (O’Brien et al.,?2009). The burden of this disease is also high in the elderly and patients with associated immunodeficiencies (Picard et al.,?2003). Bacteria make use of numerous strategies to promote their adhesion to eukaryotic cells during colonization and pathogenesis. Most Gram\positive pathogens express cell\wall surface structures, which directly or indirectly enhance bacterial interactions with host tissues, including cell adherence and invasion (Kline et al.,?2009). Extracellular matrix (ECM) components, such as collagens, fibronectin, vitronectin, fibrinogen, and plasminogen, represent fundamental targets for interactions of bacteria with host cells (Bingham et al.,?2008; Binsker et al.,?2017; Hammerschmidt et al.,?2019; Singh et al.,?2012). Collagens, the most abundant components of ECM and the main constituents Parimifasor of connective tissues, are also frequently targeted by pathogenic microbes. Collagens consist of the association of three polypeptide chains that give rise to several molecular isoforms. The 28 types of collagen recognized so far include fibril\forming and network\forming collagens. Fibril\forming collagens, such as type I, II, and III, are put together into triple\helical strands during connective tissue formation and wound healing. Network\forming collagens, such as type IV, VI, Parimifasor and X, determine the structure of basement membranes and are in direct contact with epithelial, endothelial, and muscle mass cells (Bella & Hulmes,?2017). C1q, a component of the match system, is an important a part of innate immune defenses against invading pathogens (Ricklin et al.,?2010). The C1q molecule has the shape of a blossom bouquet and is created by six identical trimeric proteins that Gpr124 associate to form the stalk and then diverge to form six stems each ending in a globular blossom head (Agarwal & Blom,?2015). Each of the six proteins consists of three polypeptides whose collagen\like domains form a characteristic triple helix structure. The globular blossom head has the function to bind antibodies as well as some acute\phase proteins, while the stalk binds to the C1r and C1s components of the match system. The binding of the globular region to pathogen\bound antibodies or acute phase proteins induces a conformational switch of C1r and activates the classical match activation pathway (Agarwal & Blom,?2015). At least two surface proteins with C1q\binding properties have been identified in to bind collagen and of the functional significance of this conversation. This pathogen was found in an early study to bind collagen type I and IV in a strain\dependent manner (Kostrzynska & Wadstrom,?1992). Moreover, collagen VI has been proposed as a putative adhesive target for pneumococcal binding to respiratory epithelium, even though.