Contribution of YjbIH to Virulence Factor Expression and Host Colonization in Staphylococcus aureus
Contribution of YjbIH to Virulence Factor Expression and Host Colonization in Staphylococcus aureus
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DOI：
10.1128/iai.00155-19
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发表时间：
2019-06-01
影响因子：
3.1
通讯作者：
Bose, Jeffrey L.
中科院分区：
文献类型：
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作者：
Austin, Crystal M.;Garabaglu, Siamak;Bose, Jeffrey L.
为了在宿主体内持续存在并引起疾病，金黄色葡萄球菌依赖于其精确微调毒力因子表达以响应快速变化的环境的能力。在无偏置转座子突变体筛选中，我们观察到双基因操纵子yjbIH的破坏导致色素沉着水平和aureolyysis （Aur）活性相对于野生型菌株降低。进一步的分析表明，YjbH（一种预测的硫氧还蛋白样氧化还原酶）是观察到的yjbIH突变表型的主要原因，尽管假定的截断血红蛋白YjbI存在次要作用。这些差异是由于crtOPQMN和aur的表达显著降低。先前的研究发现，YjbH靶向二硫化物和氧化应激反应调节因子Spx，使其被ClpXP降解。缺乏yjbH或yjbI导致对亚硝化和氧化应激以及铁剥夺的敏感性改变。此外，yjbH和yjbI突变株的乌头酸酶活性也发生了变化。在yjbH突变体中，色素沉着和aureolyysis （Aur）活性的降低是Spx依赖性的。最后，我们使用小鼠脓毒症模型来确定yjbIH缺失对发病机制的影响，发现突变体在急性感染期间比野生型菌株更能在肾脏和脾脏定植。这些研究确定了对YjbIH的色素沉着和蛋白酶活性的变化，并首次显示了这些蛋白质在感染期间的作用。
To persist within the host and cause disease, Staphylococcus aureus relies on its ability to precisely fine-tune virulence factor expression in response to rapidly changing environments. During an unbiased transposon mutant screen, we observed that disruption of a two-gene operon, yjbIH, resulted in decreased levels of pigmentation and aureolysin (Aur) activity relative to the wild-type strain. Further analyses revealed that YjbH, a predicted thioredoxin-like oxidoreductase, is predominantly responsible for the observed yjbIH mutant phenotypes, though a minor role exists for the putative truncated hemoglobin YjbI. These differences were due to significantly decreased expression of crtOPQMN and aur. Previous studies found that YjbH targets the disulfide-and oxidative stress-responsive regulator Spx for degradation by ClpXP. The absence of yjbH or yjbI resulted in altered sensitivities to nitrosative and oxidative stress and iron deprivation. Additionally, aconitase activity was altered in the yjbH and yjbI mutant strains. Decreased levels of pigmentation and aureolysin (Aur) activity in the yjbH mutant were found to be Spx dependent. Lastly, we used a murine sepsis model to determine the effect of the yjbIH deletion on pathogenesis and found that the mutant was better able to colonize the kidneys and spleens during an acute infection than the wild-type strain. These studies identified changes in pigmentation and protease activity in response to YjbIH and are the first to have shown a role for these proteins during infection.