H-NOX regulation of c-di-GMP metabolism and biofilm formation in Legionella pneumophila.

H-NOX regulation of c-di-GMP metabolism and biofilm formation in Legionella pneumophila.
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DOI:
10.1111/j.1365-2958.2010.07259.x
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发表时间:
2010-08
影响因子:
3.6
通讯作者:
Marletta MA
Marletta MA
中科院分区:
生物学2区
文献类型:
--
作者:
Carlson HK;Vance RE;Marletta MA

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血红素-一氧化氮/氧(H-NOX)结构域是一个广泛存在于细菌基因组中的血红蛋白传感器家族,但关于其功能的信息有限。嗜肺军团菌是迄今为止发现的唯一编码两种H-NOX蛋白的原核生物。本文提供了支持嗜肺军团菌H-NOXs在生物膜形成调控中的作用的数据。综上所述:(i) hnox1基因的无标记缺失不影响液体培养的生长速度或允许巨噬细胞的复制;(ii) theΔhnox1菌株表现出超生物膜表型;(iii)与hnox1相邻的基因是一种ggdefe - eal蛋白lpg1057,在嗜肺军团菌中该蛋白或已被充分研究的二光酸环化酶vca0956的过表达会导致超生物膜表型;(iv) Lpg1057蛋白在体外表现出二胍酸环化酶活性,且该活性在Fe(II)-NO连接状态下被Hnox1蛋白抑制,而在Fe(II)未连接状态下不受抑制;(v)与Hnox1对Lpg1057的调控一致,theΔhnox1背景中Lpg1057的无标记缺失导致超生物膜表型恢复到野生型生物膜水平。综上所述,这些结果表明hnox1在调节lpg1057产生c-二gmp和对NO反应的生物膜形成中的作用。
Heme Nitric oxide/OXygen (H-NOX) domains are a family of hemoprotein sensors that are widespread in bacterial genomes, but limited information is available on their function. Legionella pneumophila is the only prokaryote found thus far to encode two H-NOX proteins. This paper presents data supporting a role for one of the Legionella pneumophila H-NOXs in the regulation of biofilm formation. In summary: (i) unmarked deletions in the hnox1 gene do not affect growth rate in liquid culture or replication in permissive macrophages; (ii) theΔhnox1 strain displays a hyper-biofilm phenotype; (iii) the gene adjacent to hnox1 is a GGDEF-EAL protein, lpg1057, and overexpression in Legionella pneumophila of this protein, or the well-studied diguanylate cyclase, vca0956, results in a hyper-biofilm phenotype; (iv) the Lpg1057 protein displays diguanylate cyclase activity in vitro and this activity is inhibited by the Hnox1 protein in the Fe(II)-NO ligation state, but not the Fe(II) unligated state; (v) consistent with the Hnox1 regulation of Lpg1057, unmarked deletions of lpg1057 in theΔhnox1 background results in reversion of the hyper-biofilm phenotype back to wild-type biofilm levels. Taken together, these results suggest a role for hnox1 in regulating c-di-GMP production by lpg1057 and biofilm formation in response to NO.
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