A glutamate-alanine-leucine (EAL) domain protein of Salmonella controls bacterial survival in mice, antioxidant defence and killing of macrophages:: role of cyclic diGMP
A glutamate-alanine-leucine (EAL) domain protein of Salmonella controls bacterial survival in mice, antioxidant defence and killing of macrophages:: role of cyclic diGMP
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DOI：
10.1111/j.1365-2958.2005.04632.x
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发表时间：
2005-06-01
影响因子：
3.6
通讯作者：
Nathan, C
中科院分区：
文献类型：
--
作者：
Hisert, KB;MacCoss, M;Nathan, C
对沙门氏菌进行标记有特征序列的转座子诱变，并从野生型和免疫缺陷型小鼠中进行差异回收，结果显示此处命名为cdgR（环二鸟苷酸（c - diGMP）调节因子）的基因是该细菌在体内抵抗宿主吞噬细胞氧化酶所必需的。CdgR仅由一个谷氨酸 - 丙氨酸 - 亮氨酸（EAL）结构域组成，这是一种预测的环二鸟苷酸（c - diGMP）磷酸二酯酶。cdgR的破坏降低了细菌对过氧化氢的抵抗力，并加速了巨噬细胞对细菌的杀伤。一种超灵敏的检测方法显示野生型沙门氏菌中存在c - diGMP，且在CdgR缺陷型突变体中其水平升高。因此，除了其在调节纤维素合成和生物膜形成方面的已知作用外，细菌的c - diGMP还调节涉及抗氧化防御和细胞毒性的宿主 - 病原体相互作用。
Signature-tagged transposon mutagenesis of Salmonella with differential recovery from wild-type and immunodeficient mice revealed that the gene here named cdgR[for c-diguanylate (c-diGMP) regulator] is required for the bacterium to resist host phagocyte oxidase in vivo. CdgR consists solely of a glutamate-alanine-leucine (EAL) domain, a predicted cyclic diGMP (c-diGMP) phosphodiesterase. Disruption of cdgR decreased bacterial resistance to hydrogen peroxide and accelerated bacterial killing of macrophages. An ultrasensitive assay revealed c-diGMP in wild-type Salmonella with increased levels in the CdgR-deficient mutant. Thus, besides its known role in regulating cellulose synthesis and biofilm formation, bacterial c-diGMP also regulates host-pathogen interactions involving antioxidant defence and cytotoxicity.