Department of Molecular Medicine & Pathology, School of Medical Sciences.
Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
J Biochem. 2018 Aug 1;164(2):165-171. doi: 10.1093/jb/mvy039.
Streptococcus pyogenes nuclease A (SpnA) and streptococcal 5' nucleosidase A (S5nA) are two recently described virulence factors from the human pathogen S. pyogenes. In vitro studies have shown that SpnA is a nuclease that cleaves ssDNA and dsDNA, including the DNA backbone of neutrophil extracellular traps. S5nA was shown to hydrolyse AMP and ADP, but not ATP, to generate the immunomodulatory molecule adenosine. S5nA also generates the macrophage-toxic deoxyadenosine from dAMP. However, detailed in vivo studies of the two enzymes have been hampered by difficulties with using current animal models for this exclusive human pathogen. Here we report the identification of two novel enzymes from the fish pathogen Streptococcus iniae that show similarities to SpnA and S5nA in amino acid sequence, protein domain structure and biochemical properties. We propose that SpnAi and S5nAi are orthologues of the S. pyogenes enzymes, providing a rationale to analyse the in vivo function of the two enzymes using a S. iniae-zebrafish infection model.
化脓性链球菌核酸酶 A(SpnA)和链球菌 5' 核酸酶 A(S5nA)是人类病原体化脓性链球菌最近描述的两种毒力因子。体外研究表明,SpnA 是一种核酸酶,可切割 ssDNA 和 dsDNA,包括中性粒细胞胞外陷阱的 DNA 骨架。S5nA 被证明可水解 AMP 和 ADP,但不能水解 ATP,从而产生免疫调节分子腺苷。S5nA 还可从 dAMP 生成巨噬细胞毒性脱氧腺苷。然而,由于目前用于这种专性人类病原体的动物模型存在困难,对这两种酶的详细体内研究受到了阻碍。在这里,我们报道了从鱼类病原体杀鲑气单胞菌中鉴定出两种新型酶,它们在氨基酸序列、蛋白结构域结构和生化特性方面与 SpnA 和 S5nA 相似。我们提出 SpnAi 和 S5nAi 是化脓性链球菌酶的同源物,为使用杀鲑气单胞菌-斑马鱼感染模型分析两种酶的体内功能提供了依据。