Auto Poisoning of the Respiratory Chain by a Quorum-Sensing-Regulated Molecule Favors Biofilm Formation and Antibiotic Tolerance.

Details

Serval ID
serval:BIB_1629DCB5F3E0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Auto Poisoning of the Respiratory Chain by a Quorum-Sensing-Regulated Molecule Favors Biofilm Formation and Antibiotic Tolerance.
Journal
Current biology
Author(s)
Hazan R., Que Y.A., Maura D., Strobel B., Majcherczyk P.A., Hopper L.R., Wilbur D.J., Hreha T.N., Barquera B., Rahme L.G.
ISSN
1879-0445 (Electronic)
ISSN-L
0960-9822
Publication state
Published
Issued date
25/01/2016
Peer-reviewed
Oui
Volume
26
Number
2
Pages
195-206
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
Publication Status: ppublish
Abstract
Bacterial programmed cell death and quorum sensing are direct examples of prokaryote group behaviors, wherein cells coordinate their actions to function cooperatively like one organism for the benefit of the whole culture. We demonstrate here that 2-n-heptyl-4-hydroxyquinoline-N-oxide (HQNO), a Pseudomonas aeruginosa quorum-sensing-regulated low-molecular-weight excreted molecule, triggers autolysis by self-perturbing the electron transfer reactions of the cytochrome bc1 complex. HQNO induces specific self-poisoning by disrupting the flow of electrons through the respiratory chain at the cytochrome bc1 complex, causing a leak of reducing equivalents to O2 whereby electrons that would normally be passed to cytochrome c are donated directly to O2. The subsequent mass production of reactive oxygen species (ROS) reduces membrane potential and disrupts membrane integrity, causing bacterial cell autolysis and DNA release. DNA subsequently promotes biofilm formation and increases antibiotic tolerance to beta-lactams, suggesting that HQNO-dependent cell autolysis is advantageous to the bacterial populations. These data identify both a new programmed cell death system and a novel role for HQNO as a critical inducer of biofilm formation and antibiotic tolerance. This newly identified pathway suggests intriguing mechanistic similarities with the initial mitochondrial-mediated steps of eukaryotic apoptosis.
Keywords
Anti-Bacterial Agents/pharmacology, Bacterial Proteins/genetics, Bacterial Proteins/metabolism, Biofilms, Electron Transport/drug effects, Gene Expression Regulation, Bacterial/drug effects, Hydroxyquinolines/pharmacology, Mitochondrial Membranes/metabolism, Pseudomonas aeruginosa/drug effects, Pseudomonas aeruginosa/physiology, Quorum Sensing/drug effects, Quorum Sensing/physiology
Pubmed
Web of science
Open Access
Yes
Create date
04/12/2015 15:21
Last modification date
15/07/2020 5:22
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