An evolutionary conserved detoxification system for membrane lipid-derived peroxyl radicals in Gram-negative bacteria

• Published in: PLoS biology Vol. 20; no. 5; p. e3001610
• Main Authors: Naguib, Marwa, Feldman, Nicolás, Zarodkiewicz, Paulina, Shropshire, Holly, Biamis, Christina, El-Halfawy, Omar M, McCain, Julia, Dezanet, Clément, Décout, Jean-Luc, Chen, Yin, Cosa, Gonzalo, Valvano, Miguel A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17.05.2022; Public Library of Science (PLoS)
• Subjects: Aldehyde reductase; Aldehydes; Analysis; Antibiotics; Antimicrobial resistance; Antioxidants; Bacteria; Biology and Life Sciences; Biomarkers; Cytochrome; Cytochromes; Detoxification; Discovery Report; Evolutionary conservation; Fluorescent indicators; Genes; Genetic aspects; Genetic transcription; Gram-negative bacteria; Gram-positive bacteria; Hydrogen peroxide; Identification and classification; Lipid peroxidation; Lipids; Lipocalin; Medicine and Health Sciences; Membrane lipids; Membrane proteins; Membranes; Mutants; Norfloxacin; Nucleoside analogs; Oxidative stress; Peroxidation; Peroxyl radicals; Phospholipids; Physical Sciences; Plasmids; Polyamines; Polymyxin B; Potassium; Proteins; Radicals; Reductases; Research and Analysis Methods; Septum; United Kingdom
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.3001610

How double-membraned Gram-negative bacteria overcome lipid peroxidation is virtually unknown. Bactericidal antibiotics and superoxide ion stress stimulate the transcription of the Burkholderia cenocepacia bcnA gene that encodes a secreted lipocalin. bcnA gene orthologs are conserved in bacteria and generally linked to a conserved upstream gene encoding a cytochrome b561 membrane protein (herein named lcoA, lipocalin-associated cytochrome oxidase gene). Mutants in bcnA, lcoA, and in a gene encoding a conserved cytoplasmic aldehyde reductase (peroxidative stress-associated aldehyde reductase gene, psrA) display enhanced membrane lipid peroxidation. Compared to wild type, the levels of the peroxidation biomarker malondialdehyde (MDA) increase in the mutants upon exposure to sublethal concentrations of the bactericidal antibiotics polymyxin B and norfloxacin. Microscopy with lipid peroxidation-sensitive fluorescent probes shows that lipid peroxyl radicals accumulate at the bacterial cell poles and septum and peroxidation is associated with a redistribution of anionic phospholipids and reduced antimicrobial resistance in the mutants. We conclude that BcnA, LcoA, and PsrA are components of an evolutionary conserved, hitherto unrecognized peroxidation detoxification system that protects the bacterial cell envelope from lipid peroxyl radicals.