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Aggregating sequenc...
Aggregating sequences that occur in many proteins constitute weak spots of bacterial proteostasis
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- Khodaparast, Ladan (author)
- SWITCH Lab, Belgium; KULeuven, Belgium
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- Khodaparast, Laleh (author)
- SWITCH Lab, Belgium; KULeuven, Belgium
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- Gallardo, Rodrigo (author)
- SWITCH Lab, Belgium; KULeuven, Belgium
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- Louros, Nikolaos N. (author)
- SWITCH Lab, Belgium; KULeuven, Belgium
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- Michiels, Emiel (author)
- SWITCH Lab, Belgium; KULeuven, Belgium
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- Ramakrishnan, Reshmi (author)
- SWITCH Lab, Belgium; KULeuven, Belgium
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- Ramakers, Meine (author)
- SWITCH Lab, Belgium; KULeuven, Belgium
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- Claes, Filip (author)
- SWITCH Lab, Belgium; KULeuven, Belgium
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- Young, Lydia (author)
- Univ Leeds, England; Univ Leeds, England
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- Shahrooei, Mohammad (author)
- KULeuven, Belgium
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- Wilkinson, Hannah (author)
- SWITCH Lab, Belgium; KULeuven, Belgium
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- Desager, Matyas (author)
- SWITCH Lab, Belgium; KULeuven, Belgium
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- Tadesse, Wubishet Mengistu (author)
- KULeuven, Belgium
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- Nilsson, Peter (author)
- Linköpings universitet,Kemi,Tekniska fakulteten
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- Hammarström, Per (author)
- Linköpings universitet,Kemi,Tekniska fakulteten
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- Aertsen, Abram (author)
- KULeuven, Belgium
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- Carpentier, Sebastien (author)
- KULeuven, Belgium
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- Van Eldere, Johan (author)
- KULeuven, Belgium
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- Rousseau, Frederic (author)
- SWITCH Lab, Belgium; KULeuven, Belgium
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- Schymkowitz, Joost (author)
- SWITCH Lab, Belgium; KULeuven, Belgium
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(creator_code:org_t)
- 2018-02-28
- 2018
- English.
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9
- Related links:
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https://liu.diva-por... (primary) (Raw object)
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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Khodaparast, Lad ...
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Khodaparast, Lal ...
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Gallardo, Rodrig ...
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Louros, Nikolaos ...
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Michiels, Emiel
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Ramakrishnan, Re ...
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show more...
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Ramakers, Meine
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Claes, Filip
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Young, Lydia
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Shahrooei, Moham ...
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Wilkinson, Hanna ...
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Desager, Matyas
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Tadesse, Wubishe ...
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Nilsson, Peter
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Hammarström, Per
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Aertsen, Abram
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Carpentier, Seba ...
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Van Eldere, Joha ...
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Rousseau, Freder ...
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Schymkowitz, Joo ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Infectious Medic ...
- Articles in the publication
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Nature Communica ...
- By the university
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Linköping University