Characterization of a Bacterial Kinase That Phosphorylates Dihydrosphingosine to Form dhS1P.
Characterization of a Bacterial Kinase That Phosphorylates Dihydrosphingosine to Form dhS1P.
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DOI：
10.1128/spectrum.00002-22
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发表时间：
2022-04-27
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
与拟杆菌门的其他成员一样，口腔厌氧菌牙龈卟啉单胞菌合成多种鞘脂，类似于其人类宿主。研究表明，这些脂质（二氢神经酰胺[DHCs]）的合成与抗氧化应激、稳定期牙龈卟啉单胞菌的存活和免疫调节有关。在这里，我们构建了牙龈卟啉单胞菌菌株W83的缺失突变体，其具有编码DhSphK 1的基因的缺失，DhSphK 1是一种与真核鞘氨醇激酶（一种使鞘氨醇磷酸化以形成鞘氨醇-1-磷酸的酶）显示出高度相似性的蛋白质。我们的数据表明，dhSphK 1基因的缺失会导致牙龈卟啉单胞菌细胞的鞘脂组成发生变化;具体来说，该突变体比亲本菌株W83合成更高水平的磷酸甘油DHCs（PG-DHCs）。虽然PG 1348显示出与真核鞘氨醇激酶的高度相似性，但我们发现PG 1348酶是独特的，因为它优先磷酸化二氢鞘氨醇，而不是鞘氨醇。除了脂质组成的变化，W83 Δ PG 1348突变体还表现出细胞分裂、外膜囊泡（OMV）的生物发生和K抗原囊的量的缺陷。总之，我们已经鉴定了第一种细菌二氢鞘氨醇激酶，其活性调节牙龈卟啉单胞菌的脂质分布，并成为免疫调节的调节机制的基础。鞘氨醇磷酸盐，如鞘氨醇-1-磷酸（S1 P）和二氢鞘氨醇-1-磷酸（dhS 1 P），作为S1 P受体的配体，这种相互作用已知在介导血管生成、血管稳定性和渗透性以及免疫细胞迁移到炎症部位中发挥重要作用。研究表明，由于不同S1 P受体亚型的差异结合和激活，dhS 1 P相对于S1 P的比例向更高水平的转变改变了下游信号级联。具体来说，较高水平的dhS 1 P被认为是抗炎的。在这里，我们报告牙龈卟啉单胞菌磷酸化二氢鞘氨醇形成dhS 1 P的一种新的激酶的表征。
Like other members of the phylum Bacteroidetes, the oral anaerobe Porphyromonas gingivalis synthesizes a variety of sphingolipids, similar to its human host. Studies have shown that synthesis of these lipids (dihydroceramides [DHCs]) is involved in oxidative stress resistance, the survival of P. gingivalis during stationary phase, and immune modulation. Here, we constructed a deletion mutant of P. gingivalis strain W83 with a deletion of the gene encoding DhSphK1, a protein that shows high similarity to a eukaryotic sphingosine kinase, an enzyme that phosphorylates sphingosine to form sphingosine-1-phosphate. Our data show that deletion of the dhSphK1 gene results in a shift in the sphingolipid composition of P. gingivalis cells; specifically, the mutant synthesizes higher levels of phosphoglycerol DHCs (PG-DHCs) than the parent strain W83. Although PG1348 shows high similarity to the eukaryotic sphingosine kinase, we discovered that the PG1348 enzyme is unique, since it preferentially phosphorylates dihydrosphingosine, not sphingosine. Besides changes in lipid composition, the W83 ΔPG1348 mutant displayed a defect in cell division, the biogenesis of outer membrane vesicles (OMVs), and the amount of K antigen capsule. Taken together, we have identified the first bacterial dihydrosphingosine kinase whose activity regulates the lipid profile of P. gingivalis and underlies a regulatory mechanism of immune modulation. IMPORTANCE Sphingoid base phosphates, such as sphingosine-1-phosphate (S1P) and dihydrosphingosine-1-phosphate (dhS1P), act as ligands for S1P receptors, and this interaction is known to play a central role in mediating angiogenesis, vascular stability and permeability, and immune cell migration to sites of inflammation. Studies suggest that a shift in ratio to higher levels of dhS1P in relation to S1P alters downstream signaling cascades due to differential binding and activation of the various S1P receptor isoforms. Specifically, higher levels of dhS1P are thought to be anti-inflammatory. Here, we report on the characterization of a novel kinase in Porphyromonas gingivalis that phosphorylates dihydrosphingosine to form dhS1P.
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影响因子：
11
作者：
Duran-Pinedo, Ana E.;Chen, Tsute;Frias-Lopez, Jorge
通讯作者：
Frias-Lopez, Jorge
DOI：
10.1038/nrm.2017.107
发表时间：
2018-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Hannun YA;Obeid LM
通讯作者：
Obeid LM
影响因子：
--
作者：
Laine, ML;van Winkelhoff, AJ
通讯作者：
van Winkelhoff, AJ
影响因子：
4.4
作者：
Gardner, RG;Russell, JB;Shoemaker, NB
通讯作者：
Shoemaker, NB
影响因子：
3.1
作者：
d'Empaire, Gabriela;Baer, Michael T.;Gibson, Frank C., III
通讯作者：
Gibson, Frank C., III