Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Infect Immun. 2012 Mar;80(3):921-8. doi: 10.1128/IAI.05477-11. Epub 2011 Dec 19.
Helicobacter cinaedi, a common human intestinal bacterium, has been implicated in various enteric and systemic diseases in normal and immunocompromised patients. Protection against oxidative stress is a crucial component of bacterium-host interactions. Alkyl hydroperoxide reductase C (AhpC) is an enzyme responsible for detoxification of peroxides and is important in protection from peroxide-induced stress. H. cinaedi possesses a single ahpC, which was investigated with respect to its role in bacterial survival during oxidative stress. The H. cinaedi ahpC mutant had diminished resistance to organic hydroperoxide toxicity but increased hydrogen peroxide resistance compared with the wild-type (WT) strain. The mutant also exhibited an oxygen-sensitive phenotype and was more susceptible to killing by macrophages than the WT strain. In vivo experiments in BALB/c and BALB/c interleukin-10 (IL-10)(-/-) mice revealed that the cecal colonizing ability of the ahpC mutant was significantly reduced. The mutant also had diminished ability to induce bacterium-specific immune responses in vivo, as shown by immunoglobulin (IgG2a and IgG1) serum levels. Collectively, these data suggest that H. cinaedi ahpC not only contributes to protecting the organism against oxidative stress but also alters its pathogenic properties in vivo.
脆弱拟杆菌是人肠道内的常见细菌，与正常和免疫功能低下患者的各种肠道和全身疾病有关。抵抗氧化应激是细菌-宿主相互作用的关键组成部分。烷基氢过氧化物还原酶 C（AhpC）是一种负责解毒过氧化物的酶，对于防止过氧化物诱导的应激非常重要。脆弱拟杆菌只有一个 ahpC，本研究调查了其在细菌应对氧化应激时存活中的作用。与野生型（WT）菌株相比，脆弱拟杆菌 ahpC 突变体对有机氢过氧化物毒性的抵抗力降低，但对过氧化氢的抵抗力增加。该突变体还表现出对氧气敏感的表型，并且比 WT 菌株更容易被巨噬细胞杀死。在 BALB/c 和 BALB/c 白细胞介素-10（IL-10）（-/-）小鼠的体内实验中，发现 ahpC 突变体的定植能力显著降低。该突变体在体内诱导细菌特异性免疫反应的能力也降低，这表现为免疫球蛋白（IgG2a 和 IgG1）的血清水平。总的来说，这些数据表明脆弱拟杆菌 ahpC 不仅有助于保护机体免受氧化应激，还改变了其在体内的致病性。
