title: Burkholderia cenocepacia BC2L-C is a super lectin with dual specificity and proinflammatory activity.
abstract: Lectins and adhesins are involved in bacterial adhesion to host tissues and mucus during early steps of infection. We report the characterization of BC2L-C, a soluble lectin from the opportunistic pathogen Burkholderia cenocepacia, which has two distinct domains with unique specificities and biological activities. The N-terminal domain is a novel TNF-α-like fucose-binding lectin, while the C-terminal part is similar to a superfamily of calcium-dependent bacterial lectins. The C-terminal domain displays specificity for mannose and l-glycero-d-manno-heptose. BC2L-C is therefore a superlectin that binds independently to mannose/heptose glycoconjugates and fucosylated human histo-blood group epitopes. The apo form of the C-terminal domain crystallized as a dimer, and calcium and mannose could be docked in the binding site. The whole lectin is hexameric and the overall structure, determined by electron microscopy and small angle X-ray scattering, reveals a flexible arrangement of three mannose/heptose-specific dimers flanked by two fucose-specific TNF-α-like trimers. We propose that BC2L-C binds to the bacterial surface in a mannose/heptose-dependent manner via the C-terminal domain. The TNF-α-like domain triggers IL-8 production in cultured airway epithelial cells in a carbohydrate-independent manner, and is therefore proposed to play a role in the dysregulated proinflammatory response observed in B. cenocepacia lung infections. The unique architecture of this newly recognized superlectin correlates with multiple functions including bacterial cell cross-linking, adhesion to human epithelia, and stimulation of inflammation.
authors: CERMAV-CNRS- UPR5301 affiliated to Université Joseph Fourier, Grenoble, France.
authors: Ondřej
authors: O
authors: Sulák
authors: Gianluca
authors: G
authors: Cioci
authors: Emilie
authors: E
authors: Lameignère
authors: Viviane
authors: V
authors: Balloy
authors: Adam
authors: A
authors: Round
authors: Irina
authors: I
authors: Gutsche
authors: Lenka
authors: L
authors: Malinovská
authors: Michel
authors: M
authors: Chignard
authors: Paul
authors: P
authors: Kosma
authors: Daniel F
authors: DF
authors: Aubert
authors: Cristina L
authors: CL
authors: Marolda
authors: Miguel A
authors: MA
authors: Valvano
authors: Michaela
authors: M
authors: Wimmerová
authors: Anne
authors: A
authors: Imberty
mesh_terms: D000595:Amino Acid Sequence; D057508:Burkholderia cenocepacia; D018360:Crystallography, X-Ray; D005643:Fucose / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D016209:Interleukin-8; D037102:Lectins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D037241:Mannose-Binding Lectins / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary / Q000502:physiology; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism; D016415:Sequence Alignment; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D016209:Interleukin-8; D037102:Lectins; D037241:Mannose-Binding Lectins; D014409:Tumor Necrosis Factor-alpha; C027112:fucose-binding lectin; D005643:Fucose