Exploring new biological functions of amyloids: bacteria cell agglutination mediated by host protein aggregation

PLoS Pathog. 2012;8(11):e1003005. doi: 10.1371/journal.ppat.1003005. Epub 2012 Nov 1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Amyloid / chemistry*
  • Amyloid / genetics
  • Amyloid / immunology
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / immunology
  • Bacteria / chemistry*
  • Bacteria / genetics
  • Bacteria / immunology
  • Bacterial Infections
  • Eosinophil Cationic Protein / chemistry*
  • Eosinophil Cationic Protein / genetics
  • Eosinophil Cationic Protein / immunology
  • Humans
  • Immunity, Innate*
  • Microbial Viability*
  • Mutation, Missense

Substances

  • Amyloid
  • Anti-Bacterial Agents
  • Eosinophil Cationic Protein
  • RNASE3 protein, human

Grant support

M.T. is a recipient of an Alianza Cuatro Universidades fellowship. D.P. is a recipient of a FPU fellowship (MICINN). Microscopy experiments were carried at the Servei de Microscòpia (UAB) and fluorescence measurements at Servei d'Anàlisi i Fotodocumentació (UAB). The work was funded by MICINN (BFU2009-09371), FEDER funds and Generalitat de Catalunya (2009 SGR 795). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.