Mutations in respiratory complex I promote antibiotic persistence through alterations in intracellular acidity and protein synthesis

Abstract: Antibiotic persistence describes the presence of phenotypic variants within an isogenic bacterial population that are transiently tolerant to antibiotic treatment. Perturbations of metabolic homeostasis can promote antibiotic persistence, but the precise mechanisms are not well understood. Here, we use laboratory evolution, population-wide sequencing and biochemical characterizations to identify mutations in respiratory complex I and discover how they promote persistence in Escherichia coli.We show that persistence-inducing perturbations of metabolic homeostasis are associated with cytoplasmic acidification. Such cytoplasmic
acidification is further strengthened by compromised proton pumping in the complex I mutants. While RpoS regulon activation induces persistence in the wild type, the aggravated cytoplasmic acidification in the complex I mutants leads to increased persistence via global shutdown of protein synthesis. Thus, we propose that cytoplasmic acidification, amplified by a compromised complex I, can act as a signaling hub for perturbed metabolic homeostasis in antibiotic persisters

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Nature communications. - 13 (2022) , 546, ISSN: 2041-1723

Classification and Topics

• Classification: Biowissenschaften, Biologie

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2022
• Creator: Bergh, Bram van den ; Schramke, Hannah ; Michiels, Joran Elie ; Kimkes, Tom E. P. ; Radzikowski, Jakub Leszek ; Schimpf, Johannes ; Vedelaar, Silke R. ; Burschel, Sabrina ; Dewachter, Liselot ; Lončar, Nikola ; Schmidt, Alexander ; Meijer, Tim ; Fauvart, Maarten ; Friedrich, Thorsten ; Michiels, Jan ; Heinemann, Matthias

Further information

• DOI: 10.1038/s41467-022-28141-x
• URN: urn:nbn:de:bsz:25-freidok-2277440
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:40 AM CEST