Significance of Legionella pneumophila phospholipases for modification of lipids within the phagosomal membrane

嗜肺军团菌磷脂酶对吞噬体膜内脂质修饰的意义

• 批准号: 198259546
• 负责人: Professorin Dr. Antje Flieger
• 金额: --
• 依托单位: Fachgebiet 11: Bakterielle darmpathogene Erreger und Legionellen
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/198259546?language=en
• 关键词: Significance; Legionella; pneumophila; phospholipases; modification

Legionellae are the causative agent of Legionnaires’ disease, a potentially severe pneumonia. Phospholipases may contribute to bacterial virulence, for example via modification of eukaryotic membranes. At least 15 phospholipases A which in part also show lysophospholipase A and/or glycerolphospholipid:cholesterol acyltransferase activity have been described for L. pneumophila. Most of those activities are delivered into the host cell via type IVB (Dot/Icm) secretion, type II (Lsp) secretion, or by means of outer membrane vesicles and they might consequently be present in the Legionella-containing phagosome. It has been described that dramatic changes occur at the phagosomal membrane which is transformed into an endoplasmic reticulum-like compartment within minutes after Legionella infection. However, the lipid composition of the Legionella phagosome and whether phospholipases contribute to the lipid rearrangements is currently not known and will be investigated by the following objectives: 1.) Determination of eukaryotic target lipids of selected L. pneumophila phospholipases, 2.) Isolation of Legionella-containing phagosomes from wild type, secretion, and phospholipase mutant infections and examination of the phagosomal lipidome, 3.) Localization of specific phospholipases within an infected host cell.

军团菌是军团病的病原体，军团病是一种潜在的严重肺炎。磷脂酶可能有助于细菌的毒力，例如通过修饰真核生物膜。至少有15种磷脂酶A部分也显示溶血磷脂酶A和/或甘油磷脂：胆固醇酰基转移酶活性，已被描述为嗜肺乳杆菌。这些活性大部分通过IVB型（Dot/Icm）分泌、II型（Lsp）分泌或通过外膜囊泡传递到宿主细胞中，因此它们可能存在于含有军团菌的吞噬体中。据报道，军团菌感染后几分钟内吞噬体膜发生剧烈变化，吞噬体膜转变为内质网状样腔室。然而，军团菌吞噬体的脂质组成以及磷脂酶是否有助于脂质重排目前尚不清楚，将通过以下目的进行研究：嗜肺乳杆菌磷脂酶真核靶脂的测定[j]。从野生型、分泌型和磷脂酶突变型感染中分离含军团菌吞噬体并检测吞噬体脂质体，3)被感染宿主细胞内特定磷脂酶的定位。