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      The Role of the Bacterial Flagellum in Adhesion and Virulence

      review-article
      , *
      Biology
      MDPI
      bacterial flagella, flagellin, FliD, adhesion, invasion

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          Abstract

          The bacterial flagellum is a complex apparatus assembled of more than 20 different proteins. The flagellar basal body traverses the cell wall, whereas the curved hook connects the basal body to the whip-like flagellar filament that protrudes several µm from the bacterial cell. The flagellum has traditionally been regarded only as a motility organelle, but more recently it has become evident that flagella have a number of other biological functions. The major subunit, flagellin or FliC, of the flagellum plays a well-documented role in innate immunity and as a dominant antigen of the adaptive immune response. Importantly, flagella have also been reported to function as adhesins. Whole flagella have been indicated as significant in bacterial adhesion to and invasion into host cells. In various pathogens, e.g., Escherichia coli, Pseudomonas aeruginosa and Clostridium difficile, flagellin and/or the distally located flagellar cap protein have been reported to function as adhesins. Recently, FliC of Shiga-toxigenic E. coli was shown to be involved in cellular invasion via lipid rafts. Here, we examine the latest or most important findings regarding flagellar adhesive and invasive properties, especially focusing on the flagellum as a potential virulence factor.

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          Most cited references86

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          Coordinating assembly of a bacterial macromolecular machine.

          The assembly of large and complex organelles, such as the bacterial flagellum, poses the formidable problem of coupling temporal gene expression to specific stages of the organelle-assembly process. The discovery that levels of the bacterial flagellar regulatory protein FlgM are controlled by its secretion from the cell in response to the completion of an intermediate flagellar structure (the hook-basal body) was only the first of several discoveries of unique mechanisms that coordinate flagellar gene expression with assembly. In this Review, we discuss this mechanism, together with others that also coordinate gene regulation and flagellar assembly in Gram-negative bacteria.
            • Record: found
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            Structural basis of TLR5-flagellin recognition and signaling.

            Toll-like receptor 5 (TLR5) binding to bacterial flagellin activates signaling through the transcription factor NF-κB and triggers an innate immune response to the invading pathogen. To elucidate the structural basis and mechanistic implications of TLR5-flagellin recognition, we determined the crystal structure of zebrafish TLR5 (as a variable lymphocyte receptor hybrid protein) in complex with the D1/D2/D3 fragment of Salmonella flagellin, FliC, at 2.47 angstrom resolution. TLR5 interacts primarily with the three helices of the FliC D1 domain using its lateral side. Two TLR5-FliC 1:1 heterodimers assemble into a 2:2 tail-to-tail signaling complex that is stabilized by quaternary contacts of the FliC D1 domain with the convex surface of the opposing TLR5. The proposed signaling mechanism is supported by structure-guided mutagenesis and deletion analyses on CBLB502, a therapeutic protein derived from FliC.
              • Record: found
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              Complete atomic model of the bacterial flagellar filament by electron cryomicroscopy.

              The bacterial flagellar filament is a helical propeller for bacterial locomotion. It is a helical assembly of a single protein, flagellin, and its tubular structure is formed by 11 protofilaments in two distinct conformations, L- and R-type, for supercoiling. The X-ray crystal structure of a flagellin fragment lacking about 100 terminal residues revealed the protofilament structure, but the full filament structure is still essential for understanding the mechanism of supercoiling and polymerization. Here we report a complete atomic model of the R-type filament by electron cryomicroscopy. A density map obtained from image data up to 4 A resolution shows the feature of alpha-helical backbone and some large side chains. The atomic model built on the map reveals intricate molecular packing and an alpha-helical coiled coil formed by the terminal chains in the inner core of the filament, with its intersubunit hydrophobic interactions having an important role in stabilizing the filament.

                Author and article information

                Journal
                Biology (Basel)
                Biology (Basel)
                biology
                Biology
                MDPI
                2079-7737
                25 October 2013
                December 2013
                : 2
                : 4
                : 1242-1267
                Affiliations
                Division of General Microbiology, Department of Biosciences, University of Helsinki, P. O. Box 56, FI-00014 University of Helsinki, Finland; E-Mail: johanna.haiko@ 123456helsinki.fi
                Author notes
                [* ] Author to whom correspondence should be addressed; E-Mail: benita.westerlund@ 123456helsinki.fi ; Tel.: +358-9-19159251; Fax: +358-9-19159262.
                Article
                biology-02-01242
                10.3390/biology2041242
                4009794
                24833223
                3850cd16-c2b5-4e9a-9521-24c2494ec7b1
                © 2013 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 30 July 2013
                : 27 September 2013
                : 30 September 2013
                Categories
                Review

                bacterial flagella,flagellin,flid,adhesion,invasion
                bacterial flagella, flagellin, flid, adhesion, invasion

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