The multifaceted antibacterial mechanisms of the pioneering peptide antibiotics tyrocidine and gramicidin S
Abstract: Cyclic β-sheet decapeptides from the tyrocidine group and the homologous gramicidin S were the first commercially used antibiotics, yet it remains unclear exactly how they kill bacteria. We investigated their mode of action using a bacterial cytological profiling approach. Tyrocidines form defined ion-conducting pores, induce lipid phase separation, and strongly reduce membrane fluidity, resulting in delocalization of a broad range of peripheral and integral membrane proteins. Interestingly, they also cause DNA damage and interfere with DNA-binding proteins. Despite sharing 50% sequence identity with tyrocidines, gramicidin S causes only mild lipid demixing with minor effects on membrane fluidity and permeability. Gramicidin S delocalizes peripheral membrane proteins involved in cell division and cell envelope synthesis but does not affect integral membrane proteins or DNA. Our results shed a new light on the multifaceted antibacterial mechanisms of these antibiotics and explain why resistance to them is virtually nonexistent
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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mBio. - 9, 5 (2018) , e00802-18, ISSN: 2150-7511
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2019
- Urheber
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Wenzel, Michaela
Rautenbach, Marina
Vosloo, J. Arnold
Siersma, Tjalling
Aisenbrey, Christopher H. M.
Zaitseva, Ekaterina
Laubscher, Wikus E.
Rensburg, Wilma van
Behrends, Jan C.
Bechinger, Burkhard
Hamoen, Leendert Willem
- DOI
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10.1128/mBio.00802-18
- URN
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urn:nbn:de:bsz:25-freidok-173628
- Rechteinformation
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Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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25.03.2025, 13:43 MEZ
Datenpartner
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Beteiligte
- Wenzel, Michaela
- Rautenbach, Marina
- Vosloo, J. Arnold
- Siersma, Tjalling
- Aisenbrey, Christopher H. M.
- Zaitseva, Ekaterina
- Laubscher, Wikus E.
- Rensburg, Wilma van
- Behrends, Jan C.
- Bechinger, Burkhard
- Hamoen, Leendert Willem
- Universität
Entstanden
- 2019