The ArcA regulon and oxidative stress resistance in Haemophilus influenzae.
The ArcA regulon and oxidative stress resistance in Haemophilus influenzae.
复制标题
DOI：
10.1111/j.1365-2958.2007.05747.x
复制
发表时间：
2007-06
影响因子：
3.6
通讯作者：
中科院分区：
文献类型：
--
作者：
流感嗜血杆菌在人类宿主内的生态位之间传播，预计这些生态位的氧气水平会有所不同。 ArcAB 双组分信号转导系统控制基因表达以响应生长的呼吸条件，并与细菌发病机制有关，但其机制尚不清楚。我们进行了基因组规模的研究来鉴定流感嗜血杆菌 ArcA 调节子的基因。 arcA的缺失导致呼吸链和流感嗜血杆菌部分三羧酸循环基因的无氧表达增加，并降低多胺代谢和铁螯合基因的无氧表达水平。 arcA 的缺失还导致对短暂暴露于过氧化氢的敏感性在厌氧生长后比在有氧生长后更高。阵列数据显示，先前未分配给细菌中的 ArcA 模块的 dps 基因在 arcA 突变体中表现出表达降低。 dps 的缺失导致过氧化氢敏感性，而互补则恢复了抗性，从而深入了解了之前未表征的 arcA 介导的 H2O2 抗性机制。结果表明，流感嗜血杆菌 arcA 和 dps 在先发制人地防御从低氧环境中生长到有氧暴露于过氧化氢（感染过程中吞噬细胞产生的抗菌氧化剂）的转变中发挥着作用。
Haemophilus influenzae transits between niches within the human host that are predicted to differ in oxygen levels. The ArcAB two-component signal transduction system controls gene expression in response to respiratory conditions of growth and has been implicated in bacterial pathogenesis, yet the mechanism is not understood. We undertook a genome-scale study to identify genes of the H. influenzae ArcA regulon. Deletion of arcA resulted in increased anaerobic expression of genes of the respiratory chain and of H. influenzae's partial tricarboxylic acid cycle, and decreased anaerobic expression levels of genes of polyamine metabolism, and iron sequestration. Deletion of arcA also conferred a susceptibility to transient exposure to hydrogen peroxide that was greater following anaerobic growth than after aerobic growth. Array data revealed that the dps gene, not previously assigned to the ArcA modulon in bacteria, exhibited decreased expression in the arcA mutant. Deletion of dps resulted in hydrogen peroxide sensitivity and complementation restored resistance, providing insight into the previously uncharacterized mechanism of arcA-mediated H2O2 resistance. The results indicate a role for H. influenzae arcA and dps in pre-emptive defence against transitions from growth in low oxygen environments to aerobic exposure to hydrogen peroxide, an antibacterial oxidant produced by phagocytes during infection.