Lehrstuhl für Funktionelle Genomforschung der Mikroorganismen, Heinrich-Heine-University Düsseldorf, Universitätsstraße 1, 40225, Düsseldorf, Germany.
Lehrstuhl für Molekulare Evolution, Heinrich-Heine-University Düsseldorf, Universitätsstraße 1, 40225, Düsseldorf, Germany.
Nat Commun. 2019 Oct 11;10(1):4644. doi: 10.1038/s41467-019-12419-8.
In mammalian cells, the internal and external leaflets of the plasma membrane (PM) possess different phospholipids. Phosphatidylserine (PS) is normally confined to the inner (cytoplasmic) membrane leaflet. Here we report that the adhesin CPn0473 of the human pathogenic bacterium Chlamydia pneumoniae (Cpn) binds to the PM of human cells and induces PS externalization but unexpectedly not apoptosis. PS externalization is increased in human cells exposed to infectious Cpn cells expressing increased CPn0473 and reduced in exposure to Cpn expressing decreased CPn0473. CPn0473 binds specifically to synthetic membranes carrying PS and stimulates pore formation. Asymmetric giant unilamellar vesicles (GUVs) in which PS is restricted to the inner leaflet reveal that CPn0473 induces PS externalization in the absence of other proteins. Thus our identification of CPn0473 as a bacterial PS translocator capable of specific and apoptosis-independent PS externalization during infection extends the spectrum of mechanisms intracellular pathogens use to enter host cells.
在哺乳动物细胞中，质膜（PM）的内外叶具有不同的磷脂。磷脂酰丝氨酸（PS）通常局限于内（细胞质）膜叶。在这里，我们报告称，人类病原体肺炎衣原体（Cpn）的粘附素 CPn0473 与人类细胞的 PM 结合，并诱导 PS 外翻，但出人意料的是不会引起细胞凋亡。与表达增加的 CPn0473 的感染性 Cpn 细胞接触会增加人类细胞中 PS 的外翻，而与表达减少的 CPn0473 的 Cpn 细胞接触会减少 PS 的外翻。CPn0473 特异性结合携带 PS 的合成膜，并刺激孔形成。在 PS 仅限于内叶的不对称巨单层囊泡（GUV）中，CPn0473 可在不存在其他蛋白的情况下诱导 PS 外翻。因此，我们将 CPn0473 鉴定为一种细菌 PS 转位酶，它能够在感染过程中特异性且不依赖于细胞凋亡的方式进行 PS 外翻，从而扩展了细胞内病原体进入宿主细胞所利用的机制范围。
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