#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

BC2L-C Is a Super Lectin with Dual Specificity and Proinflammatory Activity


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.


Vyšlo v časopise: BC2L-C Is a Super Lectin with Dual Specificity and Proinflammatory Activity. PLoS Pathog 7(9): e32767. doi:10.1371/journal.ppat.1002238
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002238

Souhrn

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.


Zdroje

1. MahenthiralingamEBaldwinADowsonCG 2008 Burkholderia cepacia complex bacteria: opportunistic pathogens with important natural biology. J Appl Microbiol 104 1539 1551

2. WinkelsteinJAMarinoMCJohnstonRBJrBoyleJCurnutteJ 2000 Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore) 79 155 169

3. ButlerSLDohertyCJHughesJENelsonJWGovanJR 1995 Burkholderia cepacia and cystic fibrosis: do natural environments present a potential hazard? J Clin Microbiol 33 1001 1004

4. NzulaSVandammePGovanJR 2002 Influence of taxonomic status on the in vitro antimicrobial susceptibility of the Burkholderia cepacia complex. J Antimicrob Chemother 50 265 269

5. SaldíasMSValvanoMA 2009 Interactions of Burkholderia cenocepacia and other Burkholderia cepacia complex bacteria with epithelial and phagocytic cells. Microbiology 155 2809 2817

6. LoutetSAValvanoMA 2010 A decade of Burkholderia cenocepacia virulence determinant research. Infect Immun 78 4088 4100

7. LameignereEMalinovskaLSlavikovaMDuchaudEMitchellEP 2008 Structural basis for mannose recognition by a lectin from opportunistic bacteria Burkholderia cenocepacia. Biochem J 411 307 318

8. ImbertyAWimmerovaMMitchellEPGilboa-GarberN 2004 Structures of the lectins from Pseudomonas aeruginosa: Insights into molecular basis for host glycan recognition. Microb Infect 6 222 229

9. ChemaniCImbertyAde BentzmanSPierrePWimmerováM 2009 Role of LecA and LecB lectins in Pseudomonas aeruginosa induced lung injury and effect of carbohydrates ligands. Infect Immun 77 2065 2075

10. JohanssonEMCruszSAKolomietsEButsLKadamRU 2008 Inhibition and dispersion of Pseudomonas aeruginosa biofilms by glycopeptide dendrimers targeting the fucose-specific lectin LecB. Chem Biol 15 1249 1257

11. LameignereEShiaoTCRoyRWimmerovaMDubreuilF 2010 Structural basis of the affinity for oligomannosides and analogs displayed by BC2L-A, a Burkholderia cenocepacia soluble lectin. Glycobiology 20 87 98

12. SulakOCiociGDeliaMLahmannMVarrotA 2010 A TNF-like trimeric lectin domain from Burkholderia cenocepacia with specificity for fucosylated human histo-blood group antigens. Structure 18 59 72

13. AdamJPokornaMSabinCMitchellEPImbertyA 2007 Engineering of PA-IIL lectin from Pseudomonas aeruginosa - Unravelling the role of the specificity loop for sugar preference. BMC Struct Biol 7 36

14. De SoyzaASilipoALanzettaRGovanJRMolinaroA 2008 Chemical and biological features of Burkholderia cepacia complex lipopolysaccharides. Innate Immun 14 127 144

15. MasoudHPerryMBBrissonJRUhrinDLiJ 2009 Structural elucidation of the novel core oligosaccharide from LPS of Burkholderia cepacia serogroup O4. Glycobiology 19 462 471

16. MitchellEHoulesCSudakevitzDWimmerovaMGautierC 2002 Structural basis for oligosaccharide-mediated adhesion of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients. Nature Struct Biol 9 918 921

17. PokornaMCiociGPerretSRebuffetEKostlanovaN 2006 Unusual entropy-driven affinity of Chromobacterium violaceum lectin CV-IIL toward fucose and mannose. Biochemistry 45 7501 7510

18. SudakevitzDKostlanovaNBlatman-JanGMitchellEPLerrerB 2004 A new Ralstonia solanacearum high affinity mannose-binding lectin RS-IIL structurally resembling the Pseudomonas aeruginosa fucose-specific lectin PA-IIL. Mol Microbiol 52 691 700

19. IdeoHSekoAIshizukaIYamashitaK 2003 The N-terminal carbohydrate recognition domain of galectin-8 recognizes specific glycosphingolipids with high affinity. Glycobiology 13 713 723

20. Van DammeEJNakamura-TsurutaSSmithDFOngenaertMWinterHC 2007 Phylogenetic and specificity studies of two-domain GNA-related lectins: generation of multispecificity through domain duplication and divergent evolution. Biochem J 404 51 61

21. TielkerDHackerSLorisRStrathmannMWingenderJ 2005 Pseudomonas aeruginosa lectin LecB is located in the outer membrane and is involved in biofilm formation. Microbiology 151 1313 1323

22. BartelsKMFunkenHKnappABrockerMBottM 2011 Glycosylation is required for outer membrane localization of the lectin LecB in Pseudomonas aeruginosa. J Bacteriol in press doi:10.1128/JB.01507-01510

23. ThomasWETrintchinaEForeroMVogelVSokurenkoEV 2002 Bacterial adhesion to target cells enhanced by shear force. Cell 109 913 923

24. FinkJSteerJHJoyceDAMcWilliamASStewartGA 2003 Pro-inflammatory effects of Burkholderia cepacia on cystic fibrosis respiratory epithelium. FEMS Immunol Med Microbiol 38 273 282

25. de C. VenturaGMLe GofficRBalloyVPlotkowskiMCChignardM 2008 TLR 5, but neither TLR2 nor TLR4, is involved in lung epithelial cell response to Burkholderia cenocepacia. FEMS Immunol Med Microbiol 54 37 44

26. SajjanUSHershensonMBForstnerJFLiPumaJJ 2008 Burkholderia cenocepacia ET12 strain activates TNFR1 signalling in cystic fibrosis airway epithelial cells. Cell Microbiol 10 188 201

27. ArtnerDStanettyCMereiterCZamyatinaAKosmaP 2011 Crystal and molecular structure of methyl L-glycero-α-D-manno-heptopyranoside, and synthesis of 1->7 linked L-glycero-α-D-manno-heptobiose and its methyl-α-glycoside. Carbohydr. Res. in press (DOI: 10.1016/j.carres.2011.05.033)

28. ReiterAZamyatinaASchindlHHofingerAKosmaP 1999 Synthesis of Pseudomonas aeruginosa lipopolysaccharide core antigens containing 7-O-carbamoyl-L-glycero-D-manno-heptopyranosyl residues. Carbohydr Res 317 39 52

29. WisemanTWillistonSBrandtsJFLinLN 1989 Rapid measurement of binding constants and heats of binding using a new titration calorimeter. Anal Biochem 179 131 137

30. LeslieAGW 1992 Recent changes to the MOSFLM package for processing film and image plate data. Joint CCP4 and ESF-EACMB Newsletter on Protein Crystallography 26

31. Collaborative Computational Project Number 4 1994 The CCP4 suite: programs for protein crystallography. Acta Crystallogr D Biol Crystallogr 50 760 763

32. LebedevAAVaginAAMurshudovGN 2008 Model preparation in MOLREP and examples of model improvement using X-ray data. Acta Crystallogr D Biol Crystallogr 64 33 39

33. VaginATeplyakovA 1997 MOLREP: an Automated Program for Molecular Replacement. J Appl Crystallogr 30 1022 1025

34. MurshudovGNVaginAADodsonEJ 1997 Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr D Biol Crystallogr 53 240 255

35. EmsleyPCowtanK 2004 Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 60 2126 2132

36. PerrakisAHarkiolakiMWilsonKSLamzinVS 2001 ARP/wARP and molecular replacement. Acta Crystallogr D Biol Crystallogr 57 1445 1450

37. LaskowskiRAMacarthurMWMossDSThorntonJM 1993 Procheck - a Program to Check the Stereochemical Quality of Protein Structures. J Appl Crystallogr 26 283 291

38. ImbertyAPérezS 2000 Structure, conformation and dynamics of bioactive oligosaccharides: theoretical approaches and experimental validations. Chem Rev 100 4567 4588

39. VolkovVVSvergunDI 2003 Uniqueness of ab initio shape determination in small-angle scattering. J Appl Cryst 36 860 864

40. KonarevPVPetoukhovMVSvergunDI 2001 MASSHA - a graphics system for rigid-body modelling of macromolecular complexes against solution scattering data. J Appl Cryst 34 527 532

41. LudtkeSJBaldwinPRChiuW 1999 EMAN: semiautomated software for high-resolution single-particle reconstructions. J Struct Biol 128 82 97

42. MindellJAGrigorieffN 2003 Accurate determination of local defocus and specimen tilt in electron microscopy. J Struct Biol 142 334 347

43. HeymannJBCardoneGWinklerDCStevenAC 2008 Computational resources for cryo-electron tomography in Bsoft. J Struct Biol 161 232 242

44. van HeelMHarauzGOrlovaEVSchmidtRSchatzM 1996 A new generation of the IMAGIC image processing system. J Struct Biol 116 17 24

45. FrankJRadermacherMPenczekPZhuJLiY 1996 SPIDER and WEB: processing and visualization of images in 3D electron microscopy and related fields. J Struct Biol 116 190 199

46. ShaikhTRGaoHBaxterWTAsturiasFJBoissetN 2008 SPIDER image processing for single-particle reconstruction of biological macromolecules from electron micrographs. Nature protocols 3 1941 1974

47. MaroldaCLVicarioliJValvanoMA 2004 Wzx proteins involved in biosynthesis of O antigen function in association with the first sugar of the O-specific lipopolysaccharide subunit. Microbiology 150 4095 4105

48. AubertDFFlannaganRSValvanoMA 2008 A novel sensor kinase-response regulator hybrid controls biofilm formation and type VI secretion system activity in Burkholderia cenocepacia. Infect Immun 76 1979 1991

49. FigurskiDHHelinskiDR 1979 Replication of an origin-containing derivative of plasmid RK2 dependent on a plasmid function provided in trans. Proc Natl Acad Sci U S A 76 1648 1652

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2011 Číslo 9
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#