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

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

and Laurence G. Rahme. Current Biology 26, 195–206 (2016)

Speaker: Chia-Yu Kang (康家瑜)                                 Time: 15:00~16:00, Nov. 23, 2016

Commentator: Dr. I-Hsiu Huang (黃一修老師)           Place: Room 601

Abstract

Autolysis is a type of programmed cell death in Pseudomonas aeruginosa, a clinically significant Gram-negative pathogenic bacterium. Many studies have shown that it can resist eradication by antibiotics and form biofilms to provide a benefit collective. Bacterial programmed cell death pathways can respond to environmental cues and to cell-to-cell communication signals¹ by toxin-antitoxin modules during planktonic or sessile growth. The well-studied bacterial group behavior is quorum sensing, mediated by small excreted molecules, enabling cells to coordinate their behavior in a group manner. Nevertheless, the mechanism of quorum sensing system and its biological significance remain unexplored. The authors want to know whether the certain signaling molecule participates in P. aeruginosa autolysis pathway. Here, the authors demonstrate that 2-n-heptyl-4-hydroxyquinoline-N-oxide (HQNO), a P. aeruginosa MvfR quorum-sensing-regulated small excreted molecule, induces auto-poisoning by disrupting the electrons via the respiratory chain at the cytochrome bc1 complex. Besides, HQNO inhibits the recycling of equivalents back to the Q-cycle, causing the mass production of reactive oxygen species (ROS)². This process reduces membrane potential and disrupts membrane integrity, causing bacterial autolysis and DNA release. However, excreted DNA (eDNA) is known to facilitate biofilm formation and maturation, provides structural stability and guides cell motility inside the biofilm formation³. Therefore, the authors identified both a new programmed cell death system and a novel role of HQNO as it contributes to biofilm formation, increases antibiotic tolerance and provide direct evidence process to provide a fitness benefit to survive. This newly identified pathway suggests mechanistic similarities with the initial mitochondrial-mediated steps of eukaryotic apoptosis.

References

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2.  Deziel, E., et al. Analysis of Pseudomonas aeruginosa 4-hydroxy-2-alkylquinolines (HAQs) reveals a role for 4-hydroxy-2-heptylquinoline in cell-to-cell communication. Proceedings of the National Academy of Sciences of the United States of America 101, 1339-1344 (2004).

3.  Okshevsky, M. & Meyer, R.L. The role of extracellular DNA in the establishment, maintenance and perpetuation of bacterial biofilms. Critical reviews in microbiology 41, 341-352 (2015).