Aggregating sequences that occur in many proteins constitute weak spots of bacterial proteostasis

Nat Commun. 2018 Feb 28;9(1):866. doi: 10.1038/s41467-018-03131-0.


Aggregation is a sequence-specific process, nucleated by short aggregation-prone regions (APRs) that can be exploited to induce aggregation of proteins containing the same APR. Here, we find that most APRs are unique within a proteome, but that a small minority of APRs occur in many proteins. When aggregation is nucleated in bacteria by such frequently occurring APRs, it leads to massive and lethal inclusion body formation containing a large number of proteins. Buildup of bacterial resistance against these peptides is slow. In addition, the approach is effective against drug-resistant clinical isolates of Escherichia coli and Acinetobacter baumannii, reducing bacterial load in a murine bladder infection model. Our results indicate that redundant APRs are weak points of bacterial protein homeostasis and that targeting these may be an attractive antibacterial strategy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter baumannii / genetics
  • Acinetobacter baumannii / metabolism*
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Protein Aggregates
  • Protein Folding
  • Proteome / chemistry*
  • Proteome / genetics
  • Proteome / metabolism
  • Proteostasis*


  • Bacterial Proteins
  • Protein Aggregates
  • Proteome