AvrA是鼠伤寒沙门氏菌在上皮的宿主侵袭过程中所分泌的一种蛋白质，这种蛋白质对保守的细胞促凋亡反应具有抑制作用。
在4月17日的《细胞—宿主与微生物》（Cell Host & Microbe）上，Jones等人报道了关于AvrA介导JNK通道信号的抑制作用。在封面的图像中，果蝇幼虫的眼盘形象地描述了AvrA蛋白表达的精确时空控制过程。AvrA蛋白（绿色）在响应果蝇肿瘤坏死因子ortholog Eiger组成基因表达过程中的抑制了JNK（红色）的磷酸化。
沙门氏菌是一种细菌性病原体，它们已经具备了复杂的逃避宿主的免疫防御系统的应对措施。比如分泌相关效应蛋白到哺乳动物细胞中，以搅乱宿主的免疫系统和细胞凋亡信号转导通路，从而保证自身的安然无恙。Jones等人的研究发现，在转基因果蝇和小鼠模型中，鼠伤寒沙门氏菌分泌的效应蛋白AvrA对特定的有丝分裂原活化蛋白激酶的激酶(MAPKKs)具有乙酰化酶活性，对c-Jun N-氨基末端激酶(JNK)和NF-κB信号通路具有强抑制作用。
进一步研究证实，AvrA能够抑制沙门氏菌在小鼠肠道粘膜中引起的促凋亡先天免疫反应。沙门氏菌的这种行为与其在哺乳动物宿主中的自然史完全一致，即细菌通常会引起宿主的短暂炎症，但不会破坏上皮细胞。最新研究结果表明，针对JNK信号来抑制细胞凋亡可能是胞内病原体的一个保守策略。（科学网 武彦文/编译）
生物谷推荐原始出处：
（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.
