Cyclic-di-GMP regulates lipopolysaccharide modification and contributes to Pseudomonas aeruginosa immune evasion.
Cyclic-di-GMP regulates lipopolysaccharide modification and contributes to Pseudomonas aeruginosa immune evasion.
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DOI：
10.1038/nmicrobiol.2017.27
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发表时间：
2017-03-06
影响因子：
28.3
通讯作者：
Filloux A
中科院分区：
文献类型：
--
作者：
McCarthy RR;Mazon-Moya MJ;Moscoso JA;Hao Y;Lam JS;Bordi C;Mostowy S;Filloux A
铜绿假单胞菌是一种革兰氏阴性细菌病原体，与急性和慢性感染有关。通用c-di-GMP第二信使有助于从能动的生活方式转变为弹性生物膜，如囊性纤维化肺中。SadC二鸟苷酸环化酶与这种病理适应性转变有关。在这里，我们确定了一个未被识别的SadC合作伙伴，WarA，我们表明这是一个甲基转移酶与一个假定的激酶WarB复合。我们确定WarA与c-di-GMP结合，这增强了其甲基转移酶活性。总之，WarA和WarB与双功能大肠杆菌LPS O抗原调节因子WbdD具有结构相似性。引人注目的是，WarA影响铜绿假单胞菌O抗原模式分布，并与LPS生物合成机制相互作用。已知LPS调节宿主的免疫应答，并且通过使用斑马鱼感染模型，我们将WarA与铜绿假单胞菌逃避宿主检测的能力联系起来。
Pseudomonas aeruginosa is a Gram-negative bacterial pathogen associated with acute and chronic infections. The universal c-di-GMP second messenger is instrumental in the switch from a motile lifestyle to resilient biofilm as in the cystic fibrosis lung. The SadC diguanylate cyclase is associated with this patho-adaptive transition. Here we identified an unrecognized SadC partner, WarA, which we show is a methyltransferase in complex with a putative kinase WarB. We established that WarA binds to c-di-GMP, which potentiates its methyltransferase activity. Together, WarA and WarB have structural similarities with the bi-functional Escherichia coli LPS O antigen regulator WbdD. Strikingly, WarA influences P. aeruginosa O antigen modal distribution and interacts with the LPS biogenesis machinery. LPS is known to modulate the immune response in the host, and by using a zebrafish infection model, we implicate WarA in the ability of P. aeruginosa to evade detection by the host.