Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Targeting bioenergetics is key to counteracting the drug-tolerant state of biofilm-grown bacteria

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Bacterial persisters in long-term infection: Emergence and fitness in a complex host environment

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Equine pegiviruses cause persistent infection of bone marrow and are not associated with hepatitis

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Hypermutation as an Evolutionary Mechanism for Achromobacter xylosoxidans in Cystic Fibrosis Lung Infection

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. miRNA independent hepacivirus variants suggest a strong evolutionary pressure to maintain miR-122 dependence

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Evolution of Pseudomonas aeruginosa toward higher fitness under standard laboratory conditions

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Genetic determinants of Pseudomonas aeruginosa fitness during biofilm growth

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Mining zebrafish microbiota reveals key community-level resistance against fish pathogen infection

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Monique Donnert
  • Sarah Elsheikh
  • Alejandro Arce-Rodriguez
  • Vinay Pawar
  • Peter Braubach
  • Danny Jonigk
  • Axel Haverich
  • Siegfried Weiss
  • Mathias Müsken
  • Susanne Häussler
View graph of relations

Embedded 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.

Original languageEnglish
JournalPLoS pathogens
Volume16
Issue number12
Pages (from-to)e1009126
ISSN1553-7366
DOIs
Publication statusPublished - Dec 2020

    Research areas

  • Animals, Biofilms/drug effects, Drug Tolerance/physiology, Energy Metabolism/drug effects, Humans, Mice, Mice, Inbred BALB C, Promethazine/pharmacology, Pseudomonas Infections, Pseudomonas aeruginosa/drug effects

ID: 62403710