导致女性不育的衣原体(Chlamydia),引起军团菌病的军团菌(Legionella)等都是细胞内病原体,这些病原菌能够躲避细胞内溶酶体的吞噬作用,但其具体的躲避机制研究人员一直都不甚了解。近日Fabienne  Paumet等人发现,这种躲避机制可能与病原菌所表达的SNARE-like蛋白有关。

       SNARE蛋白是真核细胞融合细胞内容物必需的蛋白质。这些蛋白一般以稳定的复合体形式出现在细胞内容物的表面,引发和细胞膜的融合。因此,衣原体和军团菌必须和细胞内的运输小泡以及细胞膜融合机制竞争,并且躲避溶酶体的破坏作用。

       研究人员测试了病原菌所表达的SNARE-like蛋白,这些蛋白可以和真核细胞SNARE蛋白相互作用,并使细胞膜融合朝着利于病原菌生存的方向改变。衣原体和军团菌表达的SNARE-like蛋白分别为IncA和IcmG/DotF,均能抑制真核细胞SNARE蛋白介导的细胞融合。

       研究人员Dr.  Paumet介绍说,根据观察结果可以看出,细胞内病原体所表达的SNARE蛋白抑制剂能够阻断溶酶体和病原菌的融合。因此,这种SNARE-like蛋白或可成为治疗诸如衣原体等这类病原微生物感染的新靶标。

 

生物谷推荐原始出处:

PLoS ONE 4(10): e7375. doi:10.1371/journal.pone.0007375

Intracellular Bacteria Encode Inhibitory SNARE-Like Proteins

Fabienne Paumet1*, Jordan Wesolowski1, Alejandro Garcia-Diaz2, Cedric Delevoye3, Nathalie Aulner4, Howard A. Shuman5, Agathe Subtil6, James E. Rothman2

1 Thomas Jefferson University, Department of Microbiology and Immunology, Philadelphia, Pennsylvania, United States of America, 2 Department of Cell Biology, Yale University, New Haven, Connecticut, United States of America, 3 Institut Curie, Structure et Compartiments Membranaires, CNRS-UMR144, Paris, France, 4 Institut Pasteur, Imagopole, Batiment Monod, Paris, France, 5 Department of Microbiology, Columbia University Medical Center, New York, New York, United States of America, 6 Institut Pasteur, Unité de Biologie des Interactions Cellulaires, CNRS-URA 2582, Paris, France

Pathogens use diverse molecular machines to penetrate host cells and manipulate intracellular vesicular trafficking. Viruses employ glycoproteins, functionally and structurally similar to the SNARE proteins, to induce eukaryotic membrane fusion. Intracellular pathogens, on the other hand, need to block fusion of their infectious phagosomes with various endocytic compartments to escape from the degradative pathway. The molecular details concerning the mechanisms underlying this process are lacking. Using both an in vitro liposome fusion assay and a cellular assay, we showed that SNARE-like bacterial proteins block membrane fusion in eukaryotic cells by directly inhibiting SNARE-mediated membrane fusion. More specifically, we showed that IncA and IcmG/DotF, two SNARE-like proteins respectively expressed by Chlamydia and Legionella, inhibit the endocytic SNARE machinery. Furthermore, we identified that the SNARE-like motif present in these bacterial proteins encodes the inhibitory function. This finding suggests that SNARE-like motifs are capable of specifically manipulating membrane fusion in a wide variety of biological environments. Ultimately, this motif may have been selected during evolution because it is an efficient structural motif for modifying eukaryotic membrane fusion and thus contribute to pathogen survival.