Membrane depolarization kills dormant Bacillus subtilis cells by generating a lethal dose of ROS
Journal article, 2024

The bactericidal activity of several antibiotics partially relies on the production of reactive oxygen species (ROS), which is generally linked to enhanced respiration and requires the Fenton reaction. Bacterial persister cells, an important cause of recurring infections, are tolerant to these antibiotics because they are in a dormant state. Here, we use Bacillus subtilis cells in stationary phase, as a model system of dormant cells, to show that pharmacological induction of membrane depolarization enhances the antibiotics’ bactericidal activity and also leads to ROS production. However, in contrast to previous studies, this results primarily in production of superoxide radicals and does not require the Fenton reaction. Genetic analyzes indicate that Rieske factor QcrA, the iron-sulfur subunit of respiratory complex III, seems to be a primary source of superoxide radicals. Interestingly, the membrane distribution of QcrA changes upon membrane depolarization, suggesting a dissociation of complex III. Thus, our data reveal an alternative mechanism by which antibiotics can cause lethal ROS levels, and may partially explain why membrane-targeting antibiotics are effective in eliminating persisters.

Author

Declan Alan Gray

CARe

University of Gothenburg

Newcastle University

Biwen Wang

Swammerdam Institute for Life Sciences

Margareth Sidarta

Chalmers, Life Sciences, Chemical Biology

CARe

Fabián A. Cornejo

Max Planck Society

Jurian Wijnheijmer

Swammerdam Institute for Life Sciences

Rupa Rani

Chalmers, Life Sciences, Chemical Biology

CARe

Pamela Gamba

Charles River UK Ltd.

Newcastle University

K. Turgay

Max Planck Society

University of Hanover

Michaela Wenzel

Chalmers, Life Sciences, Chemical Biology

CARe

Henrik Strahl

Newcastle University

Leendert W. Hamoen

Newcastle University

Swammerdam Institute for Life Sciences

Nature Communications

2041-1723 (ISSN) 20411723 (eISSN)

Vol. 15 1 6877

Interaction of antibiotics with bacterial cells

Chalmers, 2024-01-01 -- 2026-12-31.

Chalmers, 2019-09-02 -- 2023-08-31.

Antibiotic-induced amino acid release - A new antimicrobial strategy?

Swedish Research Council (VR) (2019-04521), 2020-01-01 -- 2024-12-31.

Subject Categories (SSIF 2011)

Microbiology

Microbiology in the medical area

DOI

10.1038/s41467-024-51347-0

PubMed

39128925

More information

Latest update

3/17/2025