An evolutionary conserved detoxification system for membrane lipid-derived peroxyl radicals in Gram-negative bacteria.
An evolutionary conserved detoxification system for membrane lipid-derived peroxyl radicals in Gram-negative bacteria.
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DOI：
10.1371/journal.pbio.3001610
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发表时间：
2022-05
期刊：
影响因子：
9.8
通讯作者：
中科院分区：
文献类型：
--
作者：
双膜革兰氏阴性细菌如何克服脂质过氧化几乎是未知的。杀菌抗生素和超氧离子胁迫刺激伯克霍尔德氏菌BCNA基因的转录，该基因编码一种分泌的Lipocalin。BCNA基因同源基因在细菌中是保守的，通常与编码细胞色素b561膜蛋白的保守上游基因连锁(这里称为lcoA，Lipocalin相关细胞色素氧化酶基因)。BCNA、lcoA和一个保守的细胞质醛还原酶基因(过氧化应激相关醛还原酶基因，PSRA)的突变体表现出增强的膜脂过氧化作用。与野生型相比，在接触亚致死浓度的杀菌抗生素多粘菌素B和诺氟沙星时，突变体中过氧化生物标志物丙二醛(MDA)的水平增加。使用脂质过氧化敏感荧光探针的显微镜观察显示，脂质过氧化自由基聚集在细菌细胞极点和隔膜，过氧化与阴离子磷脂的重新分布和突变体中抗菌素耐药性的降低有关。我们得出结论，BCNA、LcoA和PSRA是进化保守的、迄今未被认识的过氧化解毒系统的组成部分，该系统保护细菌细胞被膜免受脂质过氧化自由基的伤害。双膜革兰氏阴性菌如何克服脂质过氧化应激？这项研究表明，周质Lipocalin、细胞膜细胞色素b561和细胞质醛还原酶是一种新的进化保守的脂质过氧化解毒系统的组成部分。
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. How do double-membraned Gram-negative bacteria overcome lipid peroxidation stress? This study shows that a periplasmic lipocalin, a membrane cytochrome b561, and a cytoplasmic aldehyde reductase are components of a novel evolutionarily conserved peroxidation detoxification system for lipid peroxyl radicals.
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