Exploring New Biological Functions of Amyloids: Bacteria Cell Agglutination Mediated by Host Protein Aggregation

English version České info

Antimicrobial proteins and peptides (AMPs) are important effectors of the innate immune system that play a vital role in the prevention of infections. Recent advances have highlighted the similarity between AMPs and amyloid proteins. Using the Eosinophil Cationic Protein as a model, we have rationalized the structure-activity relationships between amyloid aggregation and antimicrobial activity. Our results show how protein aggregation can induce bacteria agglutination and cell death. Using confocal and total internal reflection fluorescence microscopy we have tracked the formation in situ of protein amyloid-like aggregates at the bacteria surface and on membrane models. In both cases, fibrillar aggregates able to bind to amyloid diagnostic dyes were detected. Additionally, a single point mutation (Ile13 to Ala) can suppress the protein amyloid behavior, abolishing the agglutinating activity and impairing the antimicrobial action. The mutant is also defective in triggering both leakage and lipid vesicle aggregation. We conclude that ECP aggregation at the bacterial surface is essential for its cytotoxicity. Hence, we propose here a new prospective biological function for amyloid-like aggregates with potential biological relevance.

Vyšlo v časopise: Exploring New Biological Functions of Amyloids: Bacteria Cell Agglutination Mediated by Host Protein Aggregation. PLoS Pathog 8(11): e32767. doi:10.1371/journal.ppat.1003005
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003005

Souhrn

Zdroje

1. OtvosLJr (2005) Antibacterial peptides and proteins with multiple cellular targets. J Pept Sci 11: 697–706.

2. YountNY, BayerAS, XiongYQ, YeamanMR (2006) Advances in antimicrobial peptide immunobiology. Biopolymers 84: 435–458.

3. ZasloffM (2002) Antimicrobial peptides of multicellular organisms. Nature 415: 389–395.

4. HancockRE, SahlHG (2006) Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat Biotechnol 24: 1551–1557.

5. ZhangL, FallaTJ (2010) Potential therapeutic application of host defense peptides. Methods Mol Biol 618: 303–327.

6. BrogdenKA (2005) Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat Rev Microbiol 3: 238–250.

7. GottlerLM, RamamoorthyA (2009) Structure, membrane orientation, mechanism, and function of pexiganan–a highly potent antimicrobial peptide designed from magainin. Biochim Biophys Acta 1788: 1680–1686.

8. MarshEN, BuerBC, RamamoorthyA (2009) Fluorine–a new element in the design of membrane-active peptides. Mol Biosyst 5: 1143–1147.

9. RamamoorthyA (2009) Beyond NMR spectra of antimicrobial peptides: dynamical images at atomic resolution and functional insights. Solid State Nucl Magn Reson 35: 201–207.

10. ThennarasuS, HuangR, LeeDK, YangP, MaloyL, et al. (2010) Limiting an antimicrobial peptide to the lipid-water interface enhances its bacterial membrane selectivity: a case study of MSI-367. Biochemistry 49: 10595–10605.

11. PulidoD, NoguesMV, BoixE, TorrentM (2012) Lipopolysaccharide neutralization by antimicrobial peptides: a gambit in the innate host defense strategy. J Innate Immun 4: 327–336.

12. TorrentM, NoguesMV, BoixE (2012) Discovering new in silico tools for antimicrobial Peptide prediction. Curr Drug Targets 13: 1148–1157.

13. WimleyWC (2010) Describing the mechanism of antimicrobial peptide action with the interfacial activity model. ACS Chem Biol 5: 905–917.

14. NguyenLT, HaneyEF, VogelHJ (2011) The expanding scope of antimicrobial peptide structures and their modes of action. Trends Biotechnol 29: 464–472.

15. ButterfieldSM, LashuelHA (2010) Amyloidogenic protein-membrane interactions: mechanistic insight from model systems. Angew Chem Int Ed Engl 49: 5628–5654.

16. MahalkaAK, KinnunenPK (2009) Binding of amphipathic alpha-helical antimicrobial peptides to lipid membranes: lessons from temporins B and L. Biochim Biophys Acta. 1788: 1600–1609.

17. KaganBL, JangH, CaponeR, Teran ArceF, RamachandranS, et al. (2011) Antimicrobial Properties of Amyloid Peptides. Mol Pharm 9: 708–717.

18. BrenderJR, DurrUH, HeylD, BudarapuMB, RamamoorthyA (2007) Membrane fragmentation by an amyloidogenic fragment of human Islet Amyloid Polypeptide detected by solid-state NMR spectroscopy of membrane nanotubes. Biochim Biophys Acta 1768: 2026–2029.

19. BrenderJR, HartmanK, GottlerLM, CavittME, YoungstromDW, et al. (2009) Helical conformation of the SEVI precursor peptide PAP248–286, a dramatic enhancer of HIV infectivity, promotes lipid aggregation and fusion. Biophys J 97: 2474–2483.

20. BrenderJR, HartmanK, ReidKR, KennedyRT, RamamoorthyA (2008) A single mutation in the nonamyloidogenic region of islet amyloid polypeptide greatly reduces toxicity. Biochemistry 47: 12680–12688.

21. BrenderJR, LeeEL, CavittMA, GafniA, SteelDG, et al. (2008) Amyloid fiber formation and membrane disruption are separate processes localized in two distinct regions of IAPP, the type-2-diabetes-related peptide. J Am Chem Soc 130: 6424–6429.

22. NangaRP, BrenderJR, VivekanandanS, PopovychN, RamamoorthyA (2009) NMR structure in a membrane environment reveals putative amyloidogenic regions of the SEVI precursor peptide PAP(248–286). J Am Chem Soc 131: 17972–17979.

23. NangaRP, BrenderJR, XuJ, HartmanK, SubramanianV, et al. (2009) Three-dimensional structure and orientation of rat islet amyloid polypeptide protein in a membrane environment by solution NMR spectroscopy. J Am Chem Soc 131: 8252–8261.

24. PopovychN, BrenderJR, SoongR, VivekanandanS, HartmanK, et al. (2012) Site specific interaction of the polyphenol EGCG with the SEVI amyloid precursor peptide PAP(248–286). J Phys Chem B 116: 3650–3658.

25. JelinekR, KolushevaS (2005) Membrane interactions of host-defense peptides studied in model systems. Curr Protein Pept Sci 6: 103–114.

26. TangM, HongM (2009) Structure and mechanism of beta-hairpin antimicrobial peptides in lipid bilayers from solid-state NMR spectroscopy. Mol Biosyst 5: 317–322.

27. TorrentM, ValleJ, NoguesMV, BoixE, AndreuD (2011) The generation of antimicrobial peptide activity: a trade-off between charge and aggregation? Angew Chem Int Ed Engl 50: 10686–10689.

28. TorrentM, OdorizziF, NoguesMV, BoixE (2010) Eosinophil cationic protein aggregation: identification of an N-terminus amyloid prone region. Biomacromolecules 11: 1983–1990.

29. JangH, ArceFT, MustataM, RamachandranS, CaponeR, et al. (2011) Antimicrobial protegrin-1 forms amyloid-like fibrils with rapid kinetics suggesting a functional link. Biophys J 100: 1775–1783.

30. SosciaSJ, KirbyJE, WashicoskyKJ, TuckerSM, IngelssonM, et al. (2010) The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide. PLoS One 5: e9505.

31. HarrisF, DennisonSR, PhoenixDA (2012) Aberrant action of amyloidogenic host defense peptides: a new paradigm to investigate neurodegenerative disorders? FASEB J 26: 1776–1781.

32. TorrentM, AndreuD, NoguesVM, BoixE (2011) Connecting peptide physicochemical and antimicrobial properties by a rational prediction model. PLoS One 6: e16968.

33. GorrSU, SotskyJB, ShelarAP, DemuthDR (2008) Design of bacteria-agglutinating peptides derived from parotid secretory protein, a member of the bactericidal/permeability increasing-like protein family. Peptides 29: 2118–2127.

34. Van Nieuw AmerongenA, BolscherJG, VeermanEC (2004) Salivary proteins: protective and diagnostic value in cariology? Caries Res 38: 247–253.

35. PulidoD, MoussaouiM, AndreuD, NoguesMV, TorrentM, et al. (2012) Antimicrobial Action and Cell Agglutination by Eosinophil Cationic Protein Is Modulated by the Cell Wall Lipopolysaccharide Structure. Antimicrob Agents Chemother 56: 2378–2385.

36. BoixE, TorrentM, SánchezD, NoguésMV (2008) The Antipathogen Activities of Eosinophil Cationic Protein. Current Pharm Biotec 9: 141–152.

37. VengeP, BystromJ, CarlsonM, HakanssonL, KarawacjzykM, et al. (1999) Eosinophil cationic protein (ECP): molecular and biological properties and the use of ECP as a marker of eosinophil activation in disease. Clin Exp Allergy 29: 1172–1186.

38. BoixE, SalazarVA, TorrentM, PulidoD, NoguesMV, et al. (2012) Structural determinants of the eosinophil cationic protein antimicrobial activity. Biol Chem 393: 801–815.

39. TorrentM, BadiaM, MoussaouiM, SanchezD, NoguesMV, et al. (2010) Comparison of human RNase 3 and RNase 7 bactericidal action at the Gram-negative and Gram-positive bacterial cell wall. FEBS J 277: 1713–1725.

40. NavarroS, AleuJ, JimenezM, BoixE, CuchilloCM, et al. (2008) The cytotoxicity of eosinophil cationic protein/ribonuclease 3 on eukaryotic cell lines takes place through its aggregation on the cell membrane. Cell Mol Life Sci 65: 324–337.

41. TorrentM, NavarroS, MoussaouiM, NoguesMV, BoixE (2008) Eosinophil cationic protein high-affinity binding to bacteria-wall lipopolysaccharides and peptidoglycans. Biochemistry 47: 3544–3555.

42. TorrentM, PulidoD, de la TorreBG, Garcia-MayoralMF, NoguesMV, et al. (2011) Refining the eosinophil cationic protein antibacterial pharmacophore by rational structure minimization. J Med Chem 54: 5237–5244.

43. SanchezD, MoussaouiM, CarrerasE, TorrentM, NoguesV, et al. (2011) Mapping the eosinophil cationic protein antimicrobial activity by chemical and enzymatic cleavage. Biochimie 93: 331–338.

44. TorrentM, Di TommasoP, PulidoD, NoguesMV, NotredameC, et al. (2012) AMPA: an automated web server for prediction of protein antimicrobial regions. Bioinformatics 28: 130–131.

45. TorrentM, NoguesVM, BoixE (2009) A theoretical approach to spot active regions in antimicrobial proteins. BMC Bioinformatics 10: 373.

46. TorrentM, de la TorreBG, NoguesVM, AndreuD, BoixE (2009) Bactericidal and membrane disruption activities of the eosinophil cationic protein are largely retained in an N-terminal fragment. Biochem J 421: 425–434.

47. TorrentM, NoguesMV, BoixE (2011) Eosinophil cationic protein (ECP) can bind heparin and other glycosaminoglycans through its RNase active site. J Mol Recognit 24: 90–100.

48. KayedR, SokolovY, EdmondsB, McIntireTM, MiltonSC, et al. (2004) Permeabilization of lipid bilayers is a common conformation-dependent activity of soluble amyloid oligomers in protein misfolding diseases. J Biol Chem 279: 46363–46366.

49. AmbroggioEE, KimDH, SeparovicF, BarrowCJ, BarnhamKJ, et al. (2005) Surface behavior and lipid interaction of Alzheimer beta-amyloid peptide 1–42: a membrane-disrupting peptide. Biophys J 88: 2706–2713.

50. AuvynetC, El AmriC, LacombeC, BrustonF, BourdaisJ, et al. (2008) Structural requirements for antimicrobial versus chemoattractant activities for dermaseptin S9. FEBS J 275: 4134–4151.

51. KrsticD, MadhusudanA, DoehnerJ, VogelP, NotterT, et al. (2012) Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice. J Neuroinflammation 9: 151.

52. MiklossyJ (2011) Emerging roles of pathogens in Alzheimer disease. Expert Rev Mol Med 13: e30.

53. AlmeidaOP, LautenschlagerNT (2005) Dementia associated with infectious diseases. Int Psychogeriatr 17Suppl 1: S65–77.

54. NavarroS, BoixE, CuchilloCM, NoguesMV (2010) Eosinophil-induced neurotoxicity: the role of eosinophil cationic protein/RNase 3. J Neuroimmunol 227: 60–70.

55. FredensK, DahlR, VengeP (1982) The Gordon phenomenon induced by the eosinophil cationic protein and eosinophil protein X. J Allergy Clin Immunol 70: 361–366.

56. TorrentM, CuyasE, CarrerasE, NavarroS, LopezO, et al. (2007) Topography studies on the membrane interaction mechanism of the eosinophil cationic protein. Biochemistry 46: 720–733.

57. TorrentM, SanchezD, BuzonV, NoguesMV, CladeraJ, et al. (2009) Comparison of the membrane interaction mechanism of two antimicrobial RNases: RNase 3/ECP and RNase 7. Biochim Biophys Acta 1788: 1116–1125.