A periplasmic phospholipase that maintains outer membrane lipid asymmetry in Pseudomonas aeruginosa.
A periplasmic phospholipase that maintains outer membrane lipid asymmetry in Pseudomonas aeruginosa.
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DOI：
10.1073/pnas.2302546120
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发表时间：
2023-07-25
影响因子：
11.1
通讯作者：
Silhavy, Thomas J.
中科院分区：
文献类型：
--
作者：
Guest, Randi L.;Lee, Michael J.;Wang, Wei;Silhavy, Thomas J.
革兰氏阴性菌被外膜包围，外膜由外小叶中的脂多糖和内小叶中的甘油磷脂组成。这种独特的结构阻止了许多临床相关的抗生素进入细胞。在这里，我们发现高度耐抗生素病原体铜绿假单胞菌中的mlaa样蛋白PA3239（重命名为MlaZ）和假定的脂肪酶PA3238（重命名为MlaY）可以去除并降解外膜外小叶中错误定位的甘油磷脂。MlaYZ系统在模型革兰氏阴性大肠杆菌中起类似于外膜磷脂酶PldA的作用。降解外小叶甘油磷脂系统的趋同进化突出了这一过程在革兰氏阴性生理学中的重要性。革兰氏阴性菌的外膜在结构和功能上都是独特的。表面外露的外小叶由脂多糖组成，而内小叶由甘油磷脂组成。这种脂质不对称产生了机械强度，降低了膜的通透性，对许多病原体的毒力是必要的。错定位到外小叶的甘油磷脂通过Mla途径去除，该途径由外膜通道MlaA、质周脂质载体MlaC和内膜转运体MlaBDEF组成。条件致病菌铜绿假单胞菌有两个MlaA家族蛋白：PA2800和PA3239。在这里，我们发现PA2800是典型的Mla途径的一部分，而PA3239与假定的脂肪酶PA3238一起起作用。虽然单独失去任何一条途径对外膜完整性几乎没有影响，但失去这两条途径削弱了外膜通透性屏障，增加了次级代谢物pyocyanin的产生。我们认为错定位的甘油磷脂被PA3239（重命名为MlaZ）从外层小叶中移除，转移到PA3238（重命名为MlaY）并降解。该途径通过在降解前从外层小叶中去除甘油磷脂，简化了甘油磷脂降解产物的再循环。
Gram-negative bacteria are surrounded by an outer membrane consisting of lipopolysaccharide in the outer leaflet and glycerophospholipids in the inner leaflet. This unique architecture prevents many clinically relevant antibiotics from entering the cell. Here, we show that the MlaA-like protein PA3239 (renamed MlaZ) and the putative lipase PA3238 (renamed MlaY) in the highly antibiotic-resistant pathogen Pseudomonas aeruginosa remove and degrade glycerophospholipids that have mislocalized to the outer leaflet of the outer membrane. The MlaYZ system plays an analogous role to the outer membrane phospholipase PldA in the model Gram-negative Escherichia coli. Convergent evolution of systems that degrade outer leaflet glycerophospholipids highlights the importance of this process in Gram-negative physiology. The outer membrane of Gram-negative bacteria is unique in both structure and function. The surface-exposed outer leaflet is composed of lipopolysaccharide, while the inner leaflet is composed of glycerophospholipids. This lipid asymmetry creates mechanical strength, lowers membrane permeability, and is necessary for virulence in many pathogens. Glycerophospholipids that mislocalize to the outer leaflet are removed by the Mla pathway, which consists of the outer membrane channel MlaA, the periplasmic lipid carrier MlaC, and the inner membrane transporter MlaBDEF. The opportunistic pathogen Pseudomonas aeruginosa has two proteins of the MlaA family: PA2800 and PA3239. Here, we show that PA2800 is part of a canonical Mla pathway, while PA3239 functions with the putative lipase PA3238. While loss of either pathway individually has little to no effect on outer membrane integrity, loss of both pathways weakens the outer membrane permeability barrier and increases production of the secondary metabolite pyocyanin. We propose that mislocalized glycerophospholipids are removed from the outer leaflet by PA3239 (renamed MlaZ), transferred to PA3238 (renamed MlaY), and degraded. This pathway streamlines recycling of glycerophospholipid degradation products by removing glycerophospholipids from the outer leaflet prior to degradation.
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影响因子：
3.2
作者：
BRINT, JM;OHMAN, DE
通讯作者：
OHMAN, DE
影响因子：
48
作者：
Choi, KH;Gaynor, JB;Schweizer, HP
通讯作者：
Schweizer, HP
影响因子：
3.2
作者：
BROK, RGPM;BRINKMAN, E;TOMMASSEN, J
通讯作者：
TOMMASSEN, J
影响因子：
10.7
作者：
Hoang DT;Chernomor O;von Haeseler A;Minh BQ;Vinh LS
通讯作者：
Vinh LS
DOI：
10.3390/molecules26040927
发表时间：
2021-02-10
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Gonçalves T;Vasconcelos U
通讯作者：
Vasconcelos U