Auto Poisoning of the Respiratory Chain by a Quorum-Sensing-Regulated Molecule Favors Biofilm Formation and Antibiotic Tolerance
Authors: Yok Ai Que
Paul Anthony Majcherczyk
David J Wilbur
Teri N Hreha
Ronen Hazan
Benjamin Strobel
Laurence G Rahme
Laura Rose Hopper
Damien Maura
Blanca Barquera
Journal: Current Biology (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Bacterial programmed cell death; quorum sensing; Pseudomonas aeruginosa; HQNO; autolysis
Affiliations: Department of Surgery and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA; Department of Surgery, Center for Surgery, Innovation and Bioengineering, Massachusetts General Hospital, Boston, MA 02114, USA; Shriners Hospitals for Children Boston, Boston, MA 02114, USA., Department of Surgery and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA; Department of Surgery, Center for Surgery, Innovation and Bioengineering, Massachusetts General Hospital, Boston, MA 02114, USA., Department of Fundamental Microbiology, University of Lausanne, Lausanne 1015, Switzerland., Department of Chemistry, Tufts University, Medford, MA 02155, USA., Department of Biological Sciences, CBIS, Rensselaer Polytechnic Institute, 110 8(th) Street, Troy, NY 12180, USA., Department of Surgery and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA; Department of Surgery, Center for Surgery, Innovation and Bioengineering, Massachusetts General Hospital, Boston, MA 02114, USA; Shriners Hospitals for Children Boston, Boston, MA 02114, USA. Electronic address: .

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. 

Retracted: No

PubPeer comments:
 Figure 5D. * Red boxes: In the 48h row, the panels representing  pqsA- and  pqsA- + HQNO appear to show an overlap. Of note, the red signal is very different between the two panels, but the green signal is very similar. ![file] ,