期刊
NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-03131-0
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资金
- European Research Council under the European Union's Horizon Framework Programme ERC [647458]
- Flanders Institute for Biotechnology (VIB)
- University of Leuven (Industrieel Onderzoeksfonds)
- Funds for Scientific Research Flanders (FWO)
- Flanders Agency for innovation by Science and Technology (IWT, SBO) [60839]
- Federal Office for Scientific Affairs of Belgium (Belspo), IUAP [P7/16]
- Erasmus Mundus fellowship
- DBOF grant from KULeuven Research fund
- Goran Gustafsson Foundation
- Swedish Research council
- Swedish Foundation for Strategic Research
- Swedish Alzheimer Foundation
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.
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