Investigation of the Role That NADH Peroxidase Plays in Oxidative Stress Survival in Group B Streptococcus
Investigation of the Role That NADH Peroxidase Plays in Oxidative Stress Survival in Group B Streptococcus
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DOI：
10.3389/fmicb.2018.02786
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发表时间：
2018-11-20
影响因子：
5.2
通讯作者：
Manning, Shannon D.
中科院分区：
文献类型：
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作者：
Korir, Michelle L.;Flaherty, Rebecca A.;Manning, Shannon D.
巨噬细胞通过吞噬病原体并将其包含在吞噬小体中，在防御宿主感染方面发挥着重要作用，吞噬小体由严酷的杀菌环境组成。然而，许多病原体已经发展出在巨噬细胞内生存的机制，尽管存在这一挑战。B组链球菌(GBS)是引起新生儿败血症和脑膜炎的主要原因之一，是一种通过抵抗吞噬应激而存活在巨噬细胞内的病原体。虽然已经确定了一些关键的细胞内生存因素，但GBS对吞噬小体的解毒机制尚不清楚。巨噬细胞内存活过程中的转录分析显示，在感染后1小时和24小时，NADH过氧化物酶(Npx)强烈上调。Npx的缺失突变体(Delta Npx)更容易被多个吞噬体生化/氧化应激源的复合体外模型或单独的过氧化氢杀死。此外，与同基因的野生型GBS菌株相比，Delta npx菌株在人巨噬细胞内的存活受到损害，抑制巨噬细胞活性氧物种(ROS)产生的能力降低。因此，Npx很可能在巨噬细胞抵抗ROS产生的存活中发挥作用。更彻底地了解GBS是如何通过在巨噬细胞内生存来逃避免疫系统的，将有助于开发新的治疗措施。
Macrophages play an important role in defending the host against infections by engulfing pathogens and containing them inside the phagosome, which consists of a harsh microbicidal environment. However, many pathogens have developed mechanisms to survive inside macrophages despite this challenge. Group B Streptococcus (GBS), a leading cause of sepsis and meningitis in neonates, is one such pathogen that survives inside macrophages by withstanding phagosomal stress. Although a few key intracellular survival factors have been identified, the mechanisms by which GBS detoxifies the phagosome are poorly defined. Transcriptional analysis during survival inside macrophages revealed strong upregulation of a putative NADH peroxidase (npx) at 1 and 24 h post-infection. A deletion mutant of npx (Delta npx) was more susceptible to killing by a complex in vitro model of multiple phagosomal biochemical/oxidant stressors or by hydrogen peroxide alone. Moreover, compared to an isogenic wild type GBS strain, the Delta npx strain demonstrated impaired survival inside human macrophages and a reduced capacity to blunt macrophage reactive oxygen species (ROS) production. It is therefore likely that Npx plays a role in survival against ROS production in the macrophage. A more thorough understanding of how GBS evades the immune system through survival inside macrophages will aid in development of new therapeutic measures.