The multifaceted antibacterial mechanisms of the pioneering peptide antibiotics tyrocidine and gramicidin S

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dc.contributor.authorWenzel, Michaelaen_ZA
dc.contributor.authorRautenbach, Marinaen_ZA
dc.contributor.authorVosloo, J. Arnolden_ZA
dc.contributor.authorSiersma, Tjallingen_ZA
dc.contributor.authorAisenbrey, Christopher H. M.en_ZA
dc.contributor.authorZaitseva, Ekaterinaen_ZA
dc.contributor.authorLaubscher, Wikus Ernsten_ZA
dc.contributor.authorVan Rensburg, Wilmaen_ZA
dc.contributor.authorBehrends, Jan C.en_ZA
dc.contributor.authorBechinger, Burkharden_ZA
dc.contributor.authorHamoen, Leendert W.en_ZA
dc.date.accessioned2019-10-17T08:46:11Z
dc.date.available2019-10-17T08:46:11Z
dc.date.issued2018-10-09
dc.descriptionCITATION: Wenzel, M., et al. 2018. The multifaceted antibacterial mechanisms of the pioneering peptide antibiotics tyrocidine and gramicidin S. mBio, 9(5):e00802-18, doi:10.1128/mBio.00802-18.
dc.descriptionThe original publication is available at https://mbio.asm.org
dc.description.abstractENGLISH 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. IMPORTANCE Cyclic β-sheet decapeptides, such as tyrocidines and gramicidin S, were among the first antibiotics in clinical application. Although they have been used for such a long time, there is virtually no resistance to them, which has led to a renewed interest in this peptide class. Both tyrocidines and gramicidin S are thought to disrupt the bacterial membrane. However, this knowledge is mainly derived from in vitro studies, and there is surprisingly little knowledge about how these long-established antibiotics kill bacteria. Our results shed new light on the antibacterial mechanism of β-sheet peptide antibiotics and explain why they are still so effective and why there is so little resistance to them.en_ZA
dc.description.urihttps://mbio.asm.org/content/9/5/e00802-18
dc.description.versionPublisher's version
dc.format.extent20 pagesen_ZA
dc.identifier.citationWenzel, M., et al. 2018. The multifaceted antibacterial mechanisms of the pioneering peptide antibiotics tyrocidine and gramicidin S. mBio, 9(5):e00802-18, doi:10.1128/mBio.00802-18
dc.identifier.issn2150-7511 (online)
dc.identifier.otherdoi:10.1128/mBio.00802-18
dc.identifier.urihttp://hdl.handle.net/10019.1/106659
dc.language.isoen_ZAen_ZA
dc.publisherAmerican Society for Microbiologyen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectTyrocidinesen_ZA
dc.subjectAntibioticsen_ZA
dc.subjectPeptide antibioticsen_ZA
dc.subjectBacterial cell surfacesen_ZA
dc.titleThe multifaceted antibacterial mechanisms of the pioneering peptide antibiotics tyrocidine and gramicidin Sen_ZA
dc.typeArticleen_ZA
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