Aggregating sequences that occur in many proteins constitute weak spots of bacterial proteostasis
Khodaparast, L, Khodaparast, L, Gallardo, R et al. (17 more authors)
(2018)
Aggregating sequences that occur in many proteins constitute weak spots of bacterial proteostasis.
Nature Communications, 9.
866.
Abstract
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 Escherichiacoli and Acinetobacterbaumannii, 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.
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