Discovery of Salmonella trehalose phospholipids reveals functional convergence with mycobacteria.
Discovery of Salmonella trehalose phospholipids reveals functional convergence with mycobacteria.
复制标题
沙门氏菌海藻糖磷脂的发现揭示了与分枝杆菌的功能趋同。
DOI：
10.1084/jem.20181812
复制
发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Yamas
中科院分区：
文献类型：
--
作者：
Reinink,Peter;Buter,Jeffrey;Mishra,VivekK;Ishikawa,Eri;Cheng,Tan-Yun;Willemsen,PeterTJ;Porwollik,Steffen;Brennan,PatrickJ;Heinz,Eva;Mayfield,JacobA;Dougan,Gordon;vanEls,CécileA;Cerundolo,Vincenzo;Napolitani,Giorgio;Yamas
沙门氏菌是世界上最普遍的病原体之一。由于细胞壁与宿主界面，我们设计了一种脂质组学方法来揭示病原体特异性细胞壁化合物。在沙门氏菌、伤寒杆菌和伤寒杆菌之间差异表达的分子中。伤寒，我们关注的是富含inS的脂质。伤寒，因为它会引起伤寒。我们发现了一个以前未知的海藻糖磷脂家族，6,6 ' -二磷脂酰海藻糖（diPT）和6-磷脂酰海藻糖（PT）。心磷脂合成酶B （ClsB）是PT和diPT生物合成所必需的，但不是心磷脂生物合成所必需的。化学分型在评价diPT合成方面优于同源性分析。DiPT仅限于革兰氏阴性菌的一个子集：大量由ys产生。斑疹伤寒，其他致病菌感染较少，大肠杆菌感染数量不定。DiPT激活Mincle，这是一种巨噬细胞激活受体，也能识别分枝杆菌脐带因子（6,6′-海藻糖二mycolate）。因此，革兰氏阴性菌与分枝杆菌具有趋同作用。总的来说，我们发现了一种以前未知的免疫刺激物，它在医学上重要的细菌物种中有选择性地表达。
Salmonellaspecies are among the world’s most prevalent pathogens. Because the cell wall interfaces with the host, we designed a lipidomics approach to reveal pathogen-specific cell wall compounds. Among the molecules differentially expressed betweenSalmonellaParatyphi andS.Typhi, we focused on lipids that are enriched inS.Typhi, because it causes typhoid fever. We discovered a previously unknown family of trehalose phospholipids, 6,6′-diphosphatidyltrehalose (diPT) and 6-phosphatidyltrehalose (PT). Cardiolipin synthase B (ClsB) is essential for PT and diPT but not for cardiolipin biosynthesis. Chemotyping outperformedclsBhomology analysis in evaluating synthesis of diPT. DiPT is restricted to a subset of Gram-negative bacteria: large amounts are produced byS.Typhi, lower amounts by other pathogens, and variable amounts byEscherichia colistrains. DiPT activates Mincle, a macrophage activating receptor that also recognizes mycobacterial cord factor (6,6′-trehalose dimycolate). Thus, Gram-negative bacteria show convergent function with mycobacteria. Overall, we discovered a previously unknown immunostimulant that is selectively expressed among medically important bacterial species.