Rao Minxi, Smith Brian C, Marletta Michael A
Department of Chemistry, University of California, Berkeley, California, USA.
Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA.
mBio. 2015 May 5;6(3):e00206-15. doi: 10.1128/mBio.00206-15.
Nitric oxide (NO) plays an important signaling role in all domains of life. Many bacteria contain a heme-nitric oxide/oxygen binding (H-NOX) protein that selectively binds NO. These H-NOX proteins often act as sensors that regulate histidine kinase (HK) activity, forming part of a bacterial two-component signaling system that also involves one or more response regulators. In several organisms, NO binding to the H-NOX protein governs bacterial biofilm formation; however, the source of NO exposure for these bacteria is unknown. In mammals, NO is generated by the enzyme nitric oxide synthase (NOS) and signals through binding the H-NOX domain of soluble guanylate cyclase. Recently, several bacterial NOS proteins have also been reported, but the corresponding bacteria do not also encode an H-NOX protein. Here, we report the first characterization of a bacterium that encodes both a NOS and H-NOX, thus resembling the mammalian system capable of both synthesizing and sensing NO. We characterized the NO signaling pathway of the marine alphaproteobacterium Silicibacter sp. strain TrichCH4B, determining that the NOS is activated by an algal symbiont, Trichodesmium erythraeum. NO signaling through a histidine kinase-response regulator two-component signaling pathway results in increased concentrations of cyclic diguanosine monophosphate, a key bacterial second messenger molecule that controls cellular adhesion and biofilm formation. Silicibacter sp. TrichCH4B biofilm formation, activated by T. erythraeum, may be an important mechanism for symbiosis between the two organisms, revealing that NO plays a previously unknown key role in bacterial communication and symbiosis.
Bacterial nitric oxide (NO) signaling via heme-nitric oxide/oxygen binding (H-NOX) proteins regulates biofilm formation, playing an important role in protecting bacteria from oxidative stress and other environmental stresses. Biofilms are also an important part of symbiosis, allowing the organism to remain in a nutrient-rich environment. In this study, we show that in Silicibacter sp. strain TrichCH4B, NO mediates symbiosis with the alga Trichodesmium erythraeum, a major marine diazotroph. In addition, Silicibacter sp. TrichCH4B is the first characterized bacteria to harbor both the NOS and H-NOX proteins, making it uniquely capable of both synthesizing and sensing NO, analogous to mammalian NO signaling. Our study expands current understanding of the role of NO in bacterial signaling, providing a novel role for NO in bacterial communication and symbiosis.
一氧化氮（NO）在生命的所有领域都发挥着重要的信号传导作用。许多细菌含有一种血红素一氧化氮/氧结合（H-NOX）蛋白，该蛋白可选择性结合NO。这些H-NOX蛋白通常作为调节组氨酸激酶（HK）活性的传感器，构成细菌双组分信号系统的一部分，该系统还涉及一种或多种响应调节因子。在几种生物体中，NO与H-NOX蛋白的结合控制着细菌生物膜的形成；然而，这些细菌接触NO的来源尚不清楚。在哺乳动物中，NO由一氧化氮合酶（NOS）产生，并通过结合可溶性鸟苷酸环化酶的H-NOX结构域进行信号传导。最近，也报道了几种细菌NOS蛋白，但相应的细菌并未同时编码H-NOX蛋白。在此，我们报道了第一例同时编码NOS和H-NOX的细菌的特性，因此类似于能够合成和感知NO的哺乳动物系统。我们对海洋α-变形菌硅酸杆菌属TrichCH4B菌株的NO信号通路进行了表征，确定NOS由藻类共生体红海束毛藻激活。通过组氨酸激酶-响应调节因子双组分信号通路进行的NO信号传导导致环二鸟苷单磷酸浓度增加，环二鸟苷单磷酸是一种关键的细菌第二信使分子，可控制细胞粘附和生物膜形成。由红海束毛藻激活的硅酸杆菌属TrichCH4B生物膜形成可能是这两种生物体之间共生的重要机制，这表明NO在细菌通讯和共生中起着先前未知的关键作用。
细菌通过血红素一氧化氮/氧结合（H-NOX）蛋白进行的一氧化氮（NO）信号传导调节生物膜形成，在保护细菌免受氧化应激和其他环境应激方面发挥着重要作用。生物膜也是共生的重要组成部分，使生物体能够留在营养丰富的环境中。在本研究中，我们表明在硅酸杆菌属TrichCH4B菌株中，NO介导与主要海洋固氮蓝藻红海束毛藻的共生。此外，硅酸杆菌属TrichCH4B是首个被表征同时含有NOS和H-NOX蛋白的细菌，使其独特地能够合成和感知NO，类似于哺乳动物的NO信号传导。我们的研究扩展了当前对NO在细菌信号传导中作用的理解，为NO在细菌通讯和共生中提供了新的作用。
