Arginine-specific mono ADP-ribosylation in vitro of antimicrobial peptides by ADP-ribosylating toxins.

Arginine-specific mono ADP-ribosylation in vitro of antimicrobial peptides by ADP-ribosylating toxins.
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通过ADP-核糖基毒素,精氨酸特异性的单ADP-核糖基化抗菌肽的体外。

DOI:
10.1371/journal.pone.0041417
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Balducci E
Balducci E
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Castagnini M;Picchianti M;Talluri E;Biagini M;Del Vecchio M;Di Procolo P;Norais N;Nardi-Dei V;Balducci E

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在致病菌用于靶向真核宿主细胞的几种毒素中,发挥ADP-核糖基化活性的蛋白质代表了一个大的和研究过的危险和潜在致命毒素家族。这些蛋白质改变细胞生理学,催化ADP-核糖单位从NAD转移到参与关键代谢途径的细胞蛋白质。在本研究中,我们测试了这些毒素中的四种对ADP-核糖基化α-和β-防御素的能力。来自霍乱弧菌的霍乱毒素(CT)和来自大肠杆菌的热不稳定肠毒素(LT)均修饰人α-防御素(HNP-1)和β-防御素-1(HBD-1),与哺乳动物单ADP-核糖基转移酶-1一样有效。铜绿假单胞菌外切酶S对HNP-1和HBD 1均无活性。脑膜炎奈瑟菌NarE识别HNP-1作为底物的能力较差,但对HBD 1完全无活性。另一方面,HNP-1强烈影响NarE抑制其转移酶活性,同时增强自身ADP核糖基化。我们的结论是,只有一些精氨酸特异性ADP-核糖基化毒素识别防御素作为底物在体外。改变抗微生物肽的生物活性的修饰可能与先天免疫应答相关。特别是,ADP-核糖基化的抗菌肽可能代表了一种新的逃逸机制,通过病原体,以促进宿主组织的定植。
Among the several toxins used by pathogenic bacteria to target eukaryotic host cells, proteins that exert ADP-ribosylation activity represent a large and studied family of dangerous and potentially lethal toxins. These proteins alter cell physiology catalyzing the transfer of the ADP-ribose unit from NAD to cellular proteins involved in key metabolic pathways. In the present study, we tested the capability of four of these toxins, to ADP-ribosylate α- and β- defensins. Cholera toxin (CT) from Vibrio cholerae and heat labile enterotoxin (LT) from Escherichia coli both modified the human α-defensin (HNP-1) and β- defensin-1 (HBD1), as efficiently as the mammalian mono-ADP-ribosyltransferase-1. Pseudomonas aeruginosa exoenzyme S was inactive on both HNP-1 and HBD1. Neisseria meningitidis NarE poorly recognized HNP-1 as a substrate but it was completely inactive on HBD1. On the other hand, HNP-1 strongly influenced NarE inhibiting its transferase activity while enhancing auto-ADP-ribosylation. We conclude that only some arginine-specific ADP-ribosylating toxins recognize defensins as substrates in vitro. Modifications that alter the biological activities of antimicrobial peptides may be relevant for the innate immune response. In particular, ADP-ribosylation of antimicrobial peptides may represent a novel escape mechanism adopted by pathogens to facilitate colonization of host tissues.
DOI: 10.1021/bi00057a017
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