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

Abstract

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.

Pan msr gene deleted strain of Salmonella Typhimurium suffers oxidative stress, depicts macromolecular damage and attenuated virulence

“…Lipids are highly prone to oxidation. MDA is a marker of lipid peroxidation 22 . We next assessed the levels of MDA in both strains.…”

Prognostic roles of a novel basement membranes-related gene signature in lung adenocarcinoma

“…However, in our current study, the overexpression of ADAMTS-15 led to a poor prognosis of patients with LUAD. Recent study has found that the expression of BCNA gene can protect bacterial cell capsule from lipid peroxidation free radicals; however, its exact roles in cancer require to be further studied ( Naguib et al, 2022 ). In our study, BCNA was risk factors, and the patients with highexpression had a poor prognosis, which provided evidence for further study in the future.…”

Temperature‐induced lipocalin‐mediated membrane integrity: Possible implications for vindoline accumulation in Catharanthus roseus leaves

“…Pertinently, analogous to animal lipocalins, plant lipocalins could also be protectively involved in the scavenging of lipid peroxidation intermediates (Boca et al, 2014). Bacterial lipocalins have also been implicated as components of an evolutionarily conserved peroxidation detoxification mechanism that protects the bacterial cell envelope from lipid peroxyl radicals (Naguib et al, 2022), and a similar protective function for plant lipocalins is highly probable. Moreover, vindoline production has been linked with reactive oxygen species burst induced by exogenous stress cues like H 2 O 2 , indicating an antioxidant function of alkaloids like vindoline in plant protection (Tang et al, 2009).…”