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In particular, we examined if peptides encoding aggregation\u2010prone sequence segments of bacterial proteins can display antimicrobial activity by initiating toxic protein aggregation in bacteria, but not in mammalian cells. Unbiased <jats:italic>in vitro<\/jats:italic> screening of aggregating peptide sequences from bacterial genomes lead to the identification of several peptides that are strongly bactericidal against methicillin\u2010resistant <jats:styled-content style=\"fixed-case\"><jats:italic>S<\/jats:italic><\/jats:styled-content><jats:italic>taphylococcus aureus<\/jats:italic>. Upon parenteral administration <jats:italic>in vivo<\/jats:italic>, the peptides cured mice from bacterial sepsis without apparent toxic side effects as judged from histological and hematological evaluation. We found that the peptides enter and accumulate in the bacterial cytosol where they cause aggregation of bacterial polypeptides. Although the precise chain of events that leads to cell death remains to be elucidated, the ability to tap into aggregation\u2010prone sequences of bacterial proteomes to elicit antimicrobial activity represents a rich and unexplored chemical space to be mined in search of novel therapeutic strategies to fight infectious diseases.<\/jats:p>","DOI":"10.1111\/mmi.13269","type":"journal-article","created":{"date-parts":[[2015,11,12]],"date-time":"2015-11-12T10:52:48Z","timestamp":1447325568000},"page":"849-865","source":"Crossref","is-referenced-by-count":53,"title":["Protein aggregation as an antibiotic design strategy"],"prefix":"10.1111","volume":"99","author":[{"given":"Natalia G.","family":"Bednarska","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Bacteriology and Mycology Department of Microbiology and Immunology KULeuven  Leuven Belgium"},{"name":"Switch Laboratory VIB  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"van Eldere","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Bacteriology and Mycology Department of Microbiology and Immunology KULeuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Gallardo","sequence":"additional","affiliation":[{"name":"Switch Laboratory VIB  Leuven Belgium"},{"name":"Switch Laboratory Department of Cellular and Molecular Medicine KULeuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok","family":"Ganesan","sequence":"additional","affiliation":[{"name":"Switch Laboratory VIB  Leuven Belgium"},{"name":"Switch Laboratory Department of Cellular and Molecular Medicine KULeuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meine","family":"Ramakers","sequence":"additional","affiliation":[{"name":"Switch Laboratory VIB  Leuven Belgium"},{"name":"Switch Laboratory Department of Cellular and Molecular Medicine KULeuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Vogel","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology Department of Microbiology and Immunology KULeuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Baatsen","sequence":"additional","affiliation":[{"name":"Department of Molecular and Developmental Genetics (VIB11 and KULeuven) Electron Microscopy Network (EMoNe)  Gasthuisberg Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Staes","sequence":"additional","affiliation":[{"name":"Department of Medical Protein Research VIB  Ghent Belgium"},{"name":"Department of Biochemistry Ghent University  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Goethals","sequence":"additional","affiliation":[{"name":"Department of Medical Protein Research VIB  Ghent Belgium"},{"name":"Department of Biochemistry Ghent University  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Hammarstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Chemistry Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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