Sensing the Messenger: Potential Roles of Cyclic-di-GMP in Rickettsial Pathogenesis.
Sensing the Messenger: Potential Roles of Cyclic-di-GMP in Rickettsial Pathogenesis.
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感知使者：环状-DI-GMP在立克发病机理中的潜在作用。
DOI：
10.3390/ijms23073853
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发表时间：
2022-03-31
影响因子：
5.6
通讯作者：
Sahni SK
中科院分区：
文献类型：
--
作者：
Narra HP;Sahni A;Sepuru KM;Alsing J;Sahni SK
引起人类立克次体病的病原菌在自然界中通过节肢动物载体传播，主要感染血管内皮细胞，导致“内皮激活”和先天性免疫应答的发生。核苷酸第二信使长期以来被认为是I型干扰素的刺激物，其中细菌环二GMP（c-di-GMP）已被牵连到控制与其他细菌和宿主细胞的通信的多个信号通路，但其在立克次体与宿主相互作用的背景下的重要性尚未被研究。在这里，我们报告说，所有立克次体基因组编码一个假定的二鸟苷酸环化酶pleD，负责合成的c-di-GMP。计算机模拟分析表明，尽管PleD的结构域结构在不同的立克次体中显然是保守的，但蛋白质组成和序列可能会有所不同。有趣的是，从强毒（Sheila Smith）和无毒（爱荷华州）的R.立克次氏体揭示了一个非同义取代，导致236位的氨基酸改变（甲硫氨酸变为异亮氨酸）。另外，先前报道的在编码pleD的基因组序列中的5-bp插入（NCBI登录号：NC_009882）不存在于我们从R.立克次体菌株希拉·史密斯。体外感染HMEC的R. rickettsii（Sheila Smith），而不是R.立克次氏体（爱荷华州）感染后24 h，pleD水平发生动态变化。因此，这些发现为c-di-GMP在确定宿主细胞对致病性立克次体的反应中的潜在重要作用提供了第一个证据。进一步研究立克次体c-di-GMP可能调节病原体毒力和宿主反应的分子机制，应揭示这种多功能细菌第二信使在疾病发病机制和人类立克次体病免疫中的作用。
Pathogenic bacteria causing human rickettsioses, transmitted in nature by arthropod vectors, primarily infect vascular endothelial cells lining the blood vessels, resulting in ‘endothelial activation’ and onset of innate immune responses. Nucleotide second messengers are long presumed to be the stimulators of type I interferons, of which bacterial cyclic-di-GMP (c-di-GMP) has been implicated in multiple signaling pathways governing communication with other bacteria and host cells, yet its importance in the context of rickettsial interactions with the host has not been investigated. Here, we report that all rickettsial genomes encode a putative diguanylate cyclase pleD, responsible for the synthesis of c-di-GMP. In silico analysis suggests that although the domain architecture of PleD is apparently well-conserved among different rickettsiae, the protein composition and sequences likely vary. Interestingly, cloning and sequencing of the pleD gene from virulent (Sheila Smith) and avirulent (Iowa) strains of R. rickettsii reveals a nonsynonymous substitution, resulting in an amino acid change (methionine to isoleucine) at position 236. Additionally, a previously reported 5-bp insertion in the genomic sequence coding for pleD (NCBI accession: NC_009882) was not present in the sequence of our cloned pleD from R. rickettsii strain Sheila Smith. In vitro infection of HMECs with R. rickettsii (Sheila Smith), but not R. rickettsii (Iowa), resulted in dynamic changes in the levels of pleD up to 24 h post-infection. These findings thus provide the first evidence for the potentially important role(s) of c-di-GMP in the determination of host-cell responses to pathogenic rickettsiae. Further studies into molecular mechanisms through which rickettsial c-di-GMP might regulate pathogen virulence and host responses should uncover the contributions of this versatile bacterial second messenger in disease pathogenesis and immunity to human rickettsioses.
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DOI：
10.1084/jem.20082874
发表时间：
2009-08-31
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
McWhirter SM;Barbalat R;Monroe KM;Fontana MF;Hyodo M;Joncker NT;Ishii KJ;Akira S;Colonna M;Chen ZJ;Fitzgerald KA;Hayakawa Y;Vance RE
通讯作者：
Vance RE
DOI：
10.1093/bioinformatics/8.3.275
发表时间：
1992-06-01
期刊：
COMPUTER APPLICATIONS IN THE BIOSCIENCES
影响因子：
--
作者：
JONES, DT;TAYLOR, WR;THORNTON, JM
通讯作者：
THORNTON, JM
DOI：
10.3390/life11010031
发表时间：
2021-01-06
期刊：
Life (Basel, Switzerland)
影响因子：
--
作者：
Mantoni F;Scribani Rossi C;Paiardini A;Di Matteo A;Cappellacci L;Petrelli R;Ricciutelli M;Paone A;Cutruzzolà F;Giardina G;Rinaldo S
通讯作者：
Rinaldo S
DOI：
10.1002/prot.10286
发表时间：
2003-02-15
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
Lovell, SC;Davis, IW;Richardson, DC
通讯作者：
Richardson, DC
影响因子：
3.1
作者：
Colonne, Punsiri M.;Eremeeva, Marina E.;Sahni, Sanjeev K.
通讯作者：
Sahni, Sanjeev K.