AvrA是鼠傷寒沙門氏菌在上皮的宿主侵襲過程中所分泌的一種蛋白質(zhì)，這種蛋白質(zhì)對(duì)保守的細(xì)胞促凋亡反應(yīng)具有抑制作用,。
在4月17日的《細(xì)胞—宿主與微生物》（Cell Host & Microbe）上,，Jones等人報(bào)道了關(guān)于AvrA介導(dǎo)JNK通道信號(hào)的抑制作用,。在封面的圖像中，果蠅幼蟲的眼盤形象地描述了AvrA蛋白表達(dá)的精確時(shí)空控制過程,。AvrA蛋白（綠色）在響應(yīng)果蠅腫瘤壞死因子ortholog Eiger組成基因表達(dá)過程中的抑制了JNK（紅色）的磷酸化,。
沙門氏菌是一種細(xì)菌性病原體，它們已經(jīng)具備了復(fù)雜的逃避宿主的免疫防御系統(tǒng)的應(yīng)對(duì)措施,。比如分泌相關(guān)效應(yīng)蛋白到哺乳動(dòng)物細(xì)胞中,，以攪亂宿主的免疫系統(tǒng)和細(xì)胞凋亡信號(hào)轉(zhuǎn)導(dǎo)通路，從而保證自身的安然無恙,。Jones等人的研究發(fā)現(xiàn),，在轉(zhuǎn)基因果蠅和小鼠模型中，鼠傷寒沙門氏菌分泌的效應(yīng)蛋白AvrA對(duì)特定的有絲分裂原活化蛋白激酶的激酶(MAPKKs)具有乙酰化酶活性,，對(duì)c-Jun N-氨基末端激酶(JNK)和NF-κB信號(hào)通路具有強(qiáng)抑制作用,。
進(jìn)一步研究證實(shí)，AvrA能夠抑制沙門氏菌在小鼠腸道粘膜中引起的促凋亡先天免疫反應(yīng),。沙門氏菌的這種行為與其在哺乳動(dòng)物宿主中的自然史完全一致,，即細(xì)菌通常會(huì)引起宿主的短暫炎癥，但不會(huì)破壞上皮細(xì)胞,。最新研究結(jié)果表明,，針對(duì)JNK信號(hào)來抑制細(xì)胞凋亡可能是胞內(nèi)病原體的一個(gè)保守策略。（科學(xué)網(wǎng) 武彥文/編譯）
生物谷推薦原始出處：
（Cell Host & Microbe）,，Vol 3, 233-244, 17 April 2008,，Rheinallt M. Jones, Andrew S. Neish
Salmonella AvrA Coordinates Suppression of Host Immune and Apoptotic Defenses via JNK Pathway Blockade
Rheinallt M. Jones,1 Huixia Wu,1 Christy Wentworth,1 Liping Luo,1 Lauren Collier-Hyams,1 and Andrew S. Neish1,
1 Epithelial Pathobiology Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
Summary
Salmonellae are bacterial pathogens that have evolved sophisticated strategies to evade host immune defenses. These strategies include the secretion of effector proteins into mammalian cells so as to subvert innate immune and apoptotic signaling pathways, thereby allowing Salmonella to avoid elimination. Here, we show that the secreted Salmonella typhimurium effector protein AvrA possesses acetyltransferase activity toward specific mitogen-activated protein kinase kinases (MAPKKs) and potently inhibits c-Jun N-terminal kinase (JNK) and NF-κB signaling pathways in both transgenic Drosophila and murine models. Furthermore, we show that AvrA dampens the proapoptotic innate immune response to Salmonella at the mouse intestinal mucosa. This activity is consistent with the natural history of Salmonella in mammalian hosts, where the bacteria elicit transient inflammation but do not destroy epithelial cells. Our findings suggest that targeting JNK signaling to dampen apoptosis may be a conserved strategy for intracellular pathogens.
