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
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
mBio. - 9, 5 (2018) , e00802-18, ISSN: 2150-7511

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2019
Urheber
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
10.1128/mBio.00802-18
URN
urn:nbn:de:bsz:25-freidok-173628
Rechteinformation
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Letzte Aktualisierung
25.03.2025, 13:43 MEZ

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  • 2019

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