Show simple item record

dc.contributor.authorDonnert, Monique
dc.contributor.authorElsheikh, Sarah
dc.contributor.authorArce-Rodriguez, Alejandro
dc.contributor.authorPawar, Vinay
dc.contributor.authorBraubach, Peter
dc.contributor.authorJonigk, Danny
dc.contributor.authorHaverich, Axel
dc.contributor.authorWeiss, Siegfried
dc.contributor.authorMüsken, Mathias
dc.contributor.authorHäussler, Susanne
dc.date.accessioned2021-04-06T09:09:49Z
dc.date.available2021-04-06T09:09:49Z
dc.date.issued2020-12-22
dc.identifier.citationPLoS Pathog. 2020 Dec 22;16(12):e1009126. doi: 10.1371/journal.ppat.1009126.en_US
dc.identifier.pmid33351859
dc.identifier.doi10.1371/journal.ppat.1009126
dc.identifier.urihttp://hdl.handle.net/10033/622819
dc.description.abstractEmbedded in an extracellular matrix, biofilm-residing bacteria are protected from diverse physicochemical insults. In accordance, in the human host the general recalcitrance of biofilm-grown bacteria hinders successful eradication of chronic, biofilm-associated infections. In this study, we demonstrate that upon addition of promethazine, an FDA approved drug, antibiotic tolerance of in vitro biofilm-grown bacteria can be abolished. We show that following the addition of promethazine, diverse antibiotics are capable of efficiently killing biofilm-residing cells at minimal inhibitory concentrations. Synergistic effects could also be observed in a murine in vivo model system. PMZ was shown to increase membrane potential and interfere with bacterial respiration. Of note, antibiotic killing activity was elevated when PMZ was added to cells grown under environmental conditions that induce low intracellular proton levels. Our results imply that biofilm-grown bacteria avoid antibiotic killing and become tolerant by counteracting intracellular alkalization through the adaptation of metabolic and transport functions. Abrogation of antibiotic tolerance by interfering with the cell's bioenergetics promises to pave the way for successful eradication of biofilm-associated infections. Repurposing promethazine as a biofilm-sensitizing drug has the potential to accelerate the introduction of new treatments for recalcitrant, biofilm-associated infections into the clinic.en_US
dc.language.isoenen_US
dc.publisherPLOSen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleTargeting bioenergetics is key to counteracting the drug-tolerant state of biofilm-grown bacteria.en_US
dc.typeArticleen_US
dc.identifier.eissn1553-7374
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalPLoS pathogensen_US
dc.source.volume16
dc.source.issue12
dc.source.beginpagee1009126
dc.source.endpage
refterms.dateFOA2021-04-06T09:09:50Z
dc.source.journaltitlePLoS pathogens
dc.source.countryUnited States


Files in this item

Thumbnail
Name:
Donnert et al.pdf
Size:
2.294Mb
Format:
PDF
Description:
Open Access publication

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International