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

• DOI: 10.1038/s41467-018-03131-0
• Publication Date: 2018-02-22T10:49:34Z
• Authors: Ladan Khodaparast; Laleh Khodaparast; Rodrigo Gallardo; Nikolaos N. Louros; Emiel Michiels; Reshmi Ramakrishnan; Meine Ramakers; Filip Claes; Lydia Young; Mohammad Shahrooei; Hannah Wilkinson; Matyas Desager; Wubishet Mengistu...; K. Peter R. Nilsson; Per Hammarström; Abram Aertsen; Sebastien Carpentier; Johan Van Eldere; Frederic Rousseau; Joost Schymkowitz
• Keywords: Proteostasis; Proteome; Acinetobacter baumannii

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 most APRs are unique within proteome, but small minority occur in many proteins. When bacteria such frequently occurring APRs, it leads massive and lethal inclusion body formation large number Buildup bacterial resistance against these peptides slow. In addition, approach effective drug-resistant clinical isolates Escherichia coli Acinetobacter baumannii, reducing load murine bladder infection model. Our results indicate redundant weak points protein homeostasis targeting may an attractive antibacterial strategy.