Curing bacterial infections with protein aggregates

Abstract

SummaryA growing number of human diseases seem to be associated with protein misfolding and deposition into aggregates. Bednarska and colleagues exploit the cytotoxic nature of protein aggregates to target bacterial infections. Protein aggregation is at the same time generic and sequence dependent; this allowed the authors to develop novel aggregationprone antimicrobial peptides that penetrate bacteria and induce a peptide specific proteostatic collapse that leads to fast bacterial death, without any observable effects on host cells. The applicability of this intriguing strategy was demonstrated by curing animal models from bacterial sepsis. Although the precise mechanisms underlying the bactericidal activity of the peptide aggregates are still not clear, there is no doubt that this approach offers an exciting therapeutic alternative to conventional antibiotics.

Membrane interactions and antimicrobial effects of layered double hydroxide nanoparticles

“…liposome flocculation in the presence of nanoparticles at intermediate coverage has been investigated previously(54), nanoparticle-induced bacteria flocculation as an antimicrobial clearing mechanism remains curiously unexplored in the literature of antimicrobial nanomaterials. This is in stark contrast to aggregation-triggered antimicrobial effects and bacterial clearance by AMPs, which has attracted considerable recent interest, and been demonstrated to represent a powerful antimicrobial mechanism for several classes of antimicrobial peptides and proteins(55)(56)(57)(58)(59)(60). Clearly, therefore, and as demonstrated in the present investigation, further attention to bacterial flocculation by nanoparticles as an antimicrobial and anti-inflammatory mechanism is warranted.…”

Anti-Biofilm Molecules Targeting Functional Amyloids

“…Another interesting strategy for treating microbial infections is based on the use of amyloidogenic peptides derived from bacterial amyloids [100]. Synthetic aggregationprone peptides from Staphylococcus epidermidis (C30, C29, Hit1, Hit50) penetrate bacteria, thus causing toxic protein aggregation of polypeptides in the cytosol, which leads to bacterial death [101].…”