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

Ronen Hazan, Yok Ai Que, Damien Maura, Benjamin Strobel, Paul Anthony Majcherczyk, Laura Rose Hopper, David J. Wilbur, Teri N. Hreha, Blanca Barquera, Laurence G. Rahme*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

126 Scopus citations

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.

Original languageAmerican English
Pages (from-to)195-206
Number of pages12
JournalCurrent Biology
Volume26
Issue number2
DOIs
StatePublished - 25 Jan 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Ltd.

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