DOI

  • Daniele Peterle
  • Giulia Pontarollo
  • Stefano Spada
  • Paola Brun
  • Luana Palazzi
  • Alexej V. Sokolov
  • Barbara Spolaore
  • Patrizia Polverino de Laureto
  • Vadim B. Vasilyev
  • Ignazio Castagliuolo
  • Vincenzo De Filippis

Aggregation of human wild-type transthyretin (hTTR), a homo-tetrameric plasma protein, leads to acquired senile systemic amyloidosis (SSA), recently recognised as a major cause of cardiomyopathies in 1–3% older adults. Fragmented hTTR is the standard composition of amyloid deposits in SSA, but the protease(s) responsible for amyloidogenic fragments generation in vivo is(are) still elusive. Here, we show that subtilisin secreted from Bacillus subtilis, a gut microbiota commensal bacterium, translocates across a simulated intestinal epithelium and cleaves hTTR both in solution and human plasma, generating the amyloidogenic fragment hTTR(59–127), which is also found in SSA amyloids in vivo. To the best of our knowledge, these findings highlight a novel pathogenic mechanism for SSA whereby increased permeability of the gut mucosa, as often occurs in elderly people, allows subtilisin (and perhaps other yet unidentified bacterial proteases) to reach the bloodstream and trigger generation of hTTR fragments, acting as seeding nuclei for preferential amyloid fibrils deposition in the heart.

Язык оригиналаанглийский
Номер статьи764
ЖурналCommunications Biology
Том3
Номер выпуска1
DOI
СостояниеОпубликовано - дек 2020

    Предметные области Scopus

  • Биохимия, генетика и молекулярная биология (все)
  • Земледелие и биологические науки (все)
  • Медицина (разное)
  • Медицина (все)

ID: 75024160