Honn Marie, Lindgren Helena, Bharath Gurram K, Sjöstedt Anders
Clinical Bacteriology, and Laboratory for Molecular Infection Medicine Sweden, Department of Clinical Microbiology, Umeå University Umeå, Sweden.
Front Cell Infect Microbiol. 2017 Jan 24;7:14. doi: 10.3389/fcimb.2017.00014. eCollection 2017.
is an intracellular bacterium and as such is expected to encounter a continuous attack by reactive oxygen species (ROS) in its intracellular habitat and efficiently coping with oxidative stress is therefore essential for its survival. The oxidative stress response system of is complex and includes multiple antioxidant enzymes and pathways, including the transcriptional regulator OxyR and the HO-decomposing enzyme catalase, encoded by . The latter is regulated by OxyR. A deletion of either of these genes, however, does not severely compromise the virulence of and we hypothesized that if the bacterium would be deficient of both catalase and OxyR, then the oxidative defense and virulence of would become severely hampered. To test this hypothesis, we generated a double deletion mutant, ΔΔ, of LVS and compared its phenotype to the parental LVS strain and the corresponding single deletion mutants. In accordance with the hypothesis, ΔΔ was distinctly more susceptible than Δ and Δ to HO, ONOO, and [Formula: see text], moreover, it hardly grew in mouse-derived BMDM or in mice, whereas Δ and Δ grew as well as LVS in BMDM and exhibited only slight attenuation in mice. Altogether, the results demonstrate the importance of catalase and OxyR for a robust oxidative stress defense system and that they act cooperatively. The lack of both functions render severely crippled to handle oxidative stress and also much attenuated for intracellular growth and virulence.
是一种胞内细菌，因此预计在其胞内生存环境中会持续受到活性氧（ROS）的攻击，所以有效应对氧化应激对其生存至关重要。的氧化应激反应系统很复杂，包括多种抗氧化酶和途径，包括转录调节因子OxyR和由编码的HO分解酶过氧化氢酶。后者受OxyR调控。然而，这些基因中的任何一个缺失都不会严重损害的毒力，我们推测如果该细菌同时缺乏过氧化氢酶和OxyR，那么的氧化防御和毒力将受到严重阻碍。为了验证这一假设，我们构建了一株LVS的双缺失突变体ΔΔ，并将其表型与亲本LVS菌株及相应的单缺失突变体进行比较。与假设一致，ΔΔ比Δ和Δ对HO、ONOO和[公式：见正文]明显更敏感，此外，它在小鼠来源的骨髓衍生巨噬细胞（BMDM）或小鼠体内几乎不生长，而Δ和Δ在BMDM中生长情况与LVS相同，在小鼠体内仅表现出轻微的毒力减弱。总之，结果证明了过氧化氢酶和OxyR对强大的氧化应激防御系统的重要性，并且它们协同发挥作用。两种功能的缺失使在应对氧化应激方面严重受损，在细胞内生长和毒力方面也大大减弱。
