Streptococcus suis DNase SsnA contributes to degradation of neutrophil extracellular traps (NETs) and evasion of NET-mediated antimicrobial activity
Streptococcus suis DNase SsnA contributes to degradation of neutrophil extracellular traps (NETs) and evasion of NET-mediated antimicrobial activity
复制标题
DOI：
10.1099/mic.0.072199-0
复制
发表时间：
2014-02-01
期刊：
影响因子：
2.8
通讯作者：
Baums, Christoph G.
中科院分区：
文献类型：
--
作者：
de Buhr, Nicole;Neumann, Ariane;Baums, Christoph G.
猪链球菌是引起猪和人不同病理的重要原因，最重要的是纤维蛋白化脓性脑膜炎。感染这种病原体的组织基本上被中性粒细胞渗透，但中性粒细胞胞外陷阱(Nets)--一种最近发现的中性粒细胞的抗菌策略--在宿主防御中性粒细胞中的功能。Suis尚未接受调查。这项工作的目的是研究链霉菌的相互作用。Suis与Net在体外。链球菌。Suis诱导猪中性粒细胞形成网状结构，并被这些网状结构捕获但不被杀死。由于Net的数量随着时间的推移而减少，我们假设Strep的一个已知的胞外DNA酶。Suis使篮网降级。尽管这种核酸酶最初被命名为Strep。Suis分泌的核酸酶A(SSnA)，本工作证明了根据LPXTG细胞壁锚定基序的表面结合和部分释放到上清液中。证实了我们的假设，在佛波酯(PMA)刺激的人中性粒细胞的检测中，一个同基因的ssnA突变体在净降解和对Net的抗菌活性的保护方面显著减弱。尽管对PMA刺激的猪中性粒细胞的检测表明，SSnA也能降解猪Net，但wt和等基因sSnA突变体之间的表型差异并不明显。由于SsnA的表达对体外生长以及在猪和人血中的存活都不是至关重要的，因此结果表明SsnA是第一个在Strep中发现的特异性净逃避因子。隋斯。
Streptococcus suis is an important cause of different pathologies in pigs and humans, most importantly fibrinosuppurative meningitis. Tissue infected with this pathogen is substantially infiltrated with neutrophils, but the function of neutrophil extracellular traps (NETs) - a more recently discovered antimicrobial strategy of neutrophils - in host defence against Strep. suis has not been investigated. The objective of this work was to investigate the interaction of Strep. suis with NETs in vitro. Strep. suis induced NET formation in porcine neutrophils and was entrapped but not killed by those NETs. As the amount of NETs decreased over time, we hypothesized that a known extracellular DNase of Strep. suis degrades NETs. Though this nuclease was originally designated Strep. suis-secreted nuclease A (SsnA), this work demonstrated surface association in accordance with an LPXTG cell wall anchor motif and partial release into the supernatant. Confirming our hypothesis, an isogenic ssnA mutant was significantly attenuated in NET degradation and in protection against the antimicrobial activity of NETs as determined in assays with phorbol myristate acetate (PMA)-stimulated human neutrophils. Though assays with PMA-stimulated porcine neutrophils suggested that SsnA also degrades porcine NETs, phenotypic differences between wt and the isogenic ssnA mutant were less distinct. As SsnA expression was crucial for neither growth in vitro nor for survival in porcine or human blood, the results indicated that SsnA is the first specific NET evasion factor to be identified in Strep. suis.