LapD在心磷脂缺乏中的重要作用
Essential Role of LapD in the Absence of Cardiolipins.
摘要(中文译文)
为维持革兰阴性菌外膜的完整性，磷脂（PL）和脂多糖（LPS）这两种必需成分的水平受到严格调控，尽管其潜在分子机制尚不清楚。细菌合成三种主要的PL，包括必需的磷脂酰乙醇胺和磷脂酰甘油，以及非必需的心磷脂（CL）。我们发现，CL合成在Δ菌株中具有条件必需性。利用这一合成致死表型，我们分离出能在高温下恢复生长的抑制因子。我们发现，编码CDP-甘油二酯合成酶的基因以及编码磷脂酰甘油磷酸合成酶的基因发生功能丧失性突变，可绕过这一致死性。此类突变降低了酸性磷脂的相对丰度——这些酸性磷脂在Δ（）菌株中原本升高——并增加了顺式异油酸的含量，而未改变LpxC的量，LpxC介导LPS生物合成的第一个关键步骤。有趣的是，过表达某些基因（其产物可抑制脂肪酸/PL合成）可克服Δ（）菌株的致死性。我们证明，PgsA与LapB共纯化，LapB调控LpxC稳定性，并作为参与PL和LPS生物合成的蛋白质（包括LapD）的枢纽。总体而言，我们的结果揭示，LapD位于LPS组装与脂肪酸/PL合成之间的调控交汇点。
Abstract
To maintain the integrity of the outer membrane of Gram-negative bacteria, such as , the levels of two essential components, phospholipids (PL) and lipopolysaccharide (LPS), are tightly regulated, although the underlying molecular mechanisms are unclear. . synthesizes three main PLs, including essential phosphatidylethanolamine and phosphatidylglycerol and nonessential cardiolipin (CL). We showed that CL synthesis is conditionally essential in Δ bacteria. Using this synthetic lethal phenotype, we isolated suppressors that rescued growth at elevated temperatures. We showed that loss-of-function mutations in encoding CDP-diglyceride synthetase, and , which encodes phosphatidylglycerophosphate synthase, bypass this lethality. Such mutations reduce the relative abundance of acidic phospholipids, which are otherwise elevated in Δ() bacteria, and increase the amounts of -vaccenic acid without altering amounts of LpxC mediating the first committed step in LPS biosynthesis. Interestingly, overexpression of genes, including and , whose products can inhibit fatty acid/PL synthesis, overcame the lethality of Δ() bacteria. We demonstrated that PgsA co-purifies with LapB, which regulates LpxC stability and acts as a hub for proteins involved in PL and LPS biosynthesis, including LapD. Overall, our results reveal that LapD is positioned at the regulatory nexus between LPS assembly and fatty acid/PL synthesis.
如何引用
AMA
Satish Raina, Akshay Maniyeri, Aravind Ayyolath, Gracjana Klein. Essential Role of LapD in the Absence of Cardiolipins.. International journal of molecular sciences. 2026; doi:10.3390/ijms27031445.
APA
Satish Raina, Akshay Maniyeri, Aravind Ayyolath, Gracjana Klein (2026). Essential Role of LapD in the Absence of Cardiolipins.. International journal of molecular sciences. https://doi.org/10.3390/ijms27031445
GB/T 7714
Satish Raina, Akshay Maniyeri, Aravind Ayyolath, Gracjana Klein. Essential Role of LapD in the Absence of Cardiolipins.[J]. International journal of molecular sciences, 2026 doi:10.3390/ijms27031445.
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