最近，由托馬斯杰弗遜大學(xué),，巴黎巴斯德研究所以及耶魯大學(xué)的研究人員組成的研究小組在PLoS ONE雜志上發(fā)表了他們的研究成果，他們發(fā)現(xiàn)一些細(xì)胞內(nèi)病原體能夠利用宿主細(xì)胞的生物學(xué)屬性來(lái)逃避細(xì)胞內(nèi)溶酶體的攻擊和破壞,。
導(dǎo)致女性不育的衣原體(Chlamydia),，引起軍團(tuán)菌病的軍團(tuán)菌(Legionella)等都是細(xì)胞內(nèi)病原體，這些病原菌能夠躲避細(xì)胞內(nèi)溶酶體的吞噬作用,，但其具體的躲避機(jī)制研究人員一直都不甚了解,。近日Fabienne Paumet等人發(fā)現(xiàn)，這種躲避機(jī)制可能與病原菌所表達(dá)的SNARE-like蛋白有關(guān),。
SNARE蛋白是真核細(xì)胞融合細(xì)胞內(nèi)容物必需的蛋白質(zhì),。這些蛋白一般以穩(wěn)定的復(fù)合體形式出現(xiàn)在細(xì)胞內(nèi)容物的表面，引發(fā)和細(xì)胞膜的融合,。因此,，衣原體和軍團(tuán)菌必須和細(xì)胞內(nèi)的運(yùn)輸小泡以及細(xì)胞膜融合機(jī)制競(jìng)爭(zhēng)，并且躲避溶酶體的破壞作用,。
研究人員測(cè)試了病原菌所表達(dá)的SNARE-like蛋白，這些蛋白可以和真核細(xì)胞SNARE蛋白相互作用，并使細(xì)胞膜融合朝著利于病原菌生存的方向改變,。衣原體和軍團(tuán)菌表達(dá)的SNARE-like蛋白分別為IncA和IcmG/DotF，均能抑制真核細(xì)胞SNARE蛋白介導(dǎo)的細(xì)胞融合,。
研究人員Dr. Paumet介紹說(shuō),，根據(jù)觀(guān)察結(jié)果可以看出，細(xì)胞內(nèi)病原體所表達(dá)的SNARE蛋白抑制劑能夠阻斷溶酶體和病原菌的融合,。因此,，這種SNARE-like蛋白或可成為治療諸如衣原體等這類(lèi)病原微生物感染的新靶標(biāo)。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
