国际口腔医学杂志

国际口腔医学杂志 ›› 2017, Vol. 44 ›› Issue (6): 647-653.doi: 10.7518/gjkq.2017.06.005

• 微生物专栏 • 上一篇    下一篇

环二腺嘌呤核苷酸信号系统及其在口腔细菌致病机制中的研究展望

程兴群, 徐欣, 周学东, 李雨庆   

  1. 口腔疾病研究国家重点实验室 国家口腔疾病临床医学研究中心 四川大学华西口腔医院 成都 610041
  • 收稿日期:2016-10-24 修回日期:2017-08-06 出版日期:2017-11-01 发布日期:2017-11-01
  • 通讯作者: 李雨庆,副教授,博士,Email：liyuqing@scu.edu.cn
  • 作者简介:程兴群,博士,Email：chengxq2007@163.com
  • 基金资助:
    国家自然科学基金（31200985,81430011）

Research progress on cyclic di-adenosine monophosphate signaling system and its potential role in oral bacterial pathogenesis

Cheng Xingqun, Xu Xin, Zhou Xuedong, Li Yuqing.   

  1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
  • Received:2016-10-24 Revised:2017-08-06 Online:2017-11-01 Published:2017-11-01
  • Supported by:
    This study was supported by National Natural Science Fundation of China(31200985, 81430011).

RichHTML

5

PDF (PC)

569

摘要： 环二腺嘌呤核苷酸（c-di-AMP）是在继环腺嘌呤核苷酸（cAMP）、四（五）磷酸鸟嘌呤核苷（(p)ppGpp）、环二鸟嘌呤核苷酸（c-di-GMP）后新发现的一种第二信使分子,在细菌和支原体中广泛存在。c-di-AMP调控细菌多项生理活动,如细胞周期、细胞壁稳定性、细胞形态、刺激宿主免疫反应以及应对外界环境胁迫等。本文总结了信使分子c-di-AMP自发现以来的研究进展,这些信息可丰富对c-di-AMP调控作用的全面理解。同时,生物信息学分析发现在口腔常见细菌（如变异链球菌和牙龈卟啉单胞菌等）基因组中均存在编码c-di-AMP合成酶的基因,对于这一类基因的功能研究将为深入认识c-di-AMP信号系统在口腔细菌致病过程中的潜在作用提供重要线索,并为研究其在口腔细菌致病性中的调控机制开辟新天地。

关键词: 环二腺嘌呤核苷酸, 口腔细菌, 信号传递, 致病机制

Abstract: Cyclic di-adenosine monophosphate(c-di-AMP) is a new signal nucleotide, widely distributed among bacteria and archaea. c-di-AMP plays an important role in the regulation of cell growth, cell wall homeostasis, interaction with host immune system and stress response. Bioinformatic analysis revealed that many oral bacterial genomes could encode the c-di-AMP synthase gene. Here we provide an overview of the synthesis and regulation of c-di-AMP in bacteria, highlighting the currently identified receptor proteins and pathways that are directly or indirectly controlled by c-di-AMP, as well as the recognition of c-di-AMP by the eukaryotic host. This review can serve as an important reference for future research of the c-di-AMP signaling system in oral bacteria.

Key words: cyclic di-adenosine monophosphate, oral bacteria, signaling transduction, pathogenesis

中图分类号: 

  • R781.4+2
[1] Witte G, Hartung S, Büttner K, et al. Structural bio-chemistry of a bacterial checkpoint protein reveals diadenylate cyclase activity regulated by DNA recombination intermediates[J]. Mol Cell, 2008, 30 (2):167-178.
[2] Jenny HC-Y, Don D, Oger J. Synthesis and physical characterization of bis 3’→5’ cyclic dinucleotides (NpNp): RNA polymerase inhibitors[J]. Nucleos Nucleot, 1985, 4(3):377-389.
[3] Bejerano-Sagie M, Oppenheimer-Shaanan Y, Berla-tzky I, et al. A checkpoint protein that scans the chromosome for damage at the start of sporulation in Bacillus subtilis [J]. Cell, 2006, 125(4):679-690.
[4] Römling U. Great times for small molecules: c-di-AMP, a second messenger candidate in Bacteria and Archaea [J]. Sci Signal, 2008, 1(33):pe39.
[5] Punta M, Coggill PC, Eberhardt RY, et al. The Pfam protein families database[J]. Nucleic Acids Res, 2012, 40(Database issue):D290-D301.
[6] Oppenheimer-Shaanan Y, Wexselblatt E, Katzhendler J, et al. c-di-AMP reports DNA integrity during sporulation in Bacillus subtilis [J]. EMBO Rep, 2011, 12(6):594-601.
[7] Luo Y, Helmann JD. Analysis of the role of Bacillus subtilis σ(M) in β-lactam resistance reveals an essen-tial role for c-di-AMP in peptidoglycan homeostasis [J]. Mol Microbiol, 2012, 83(3):623-639.
[8] Mehne FM, Schröder-Tittmann K, Eijlander RT, et al. Control of the diadenylate cyclase CdaS in Baci - llus subtilis : an autoinhibitory domain limits cyclic di-AMP production[J]. J Biol Chem, 2014, 289 (30):21098-21107.
[9] Woodward JJ, Iavarone AT, Portnoy DA. c-di-AMP secreted by intracellular Listeria monocytogenes activates a host typeⅠinterferon response[J]. Science, 2010, 328(5986):1703-1705.
[10] Schwartz KT, Carleton JD, Quillin SJ, et al. Hy-perinduction of host beta interferon by a Listeria monocytogenes strain naturally overexpressing the multidrug efflux pump MdrT[J]. Infect Immun, 2012, 80(4):1537-1545.
[11] Whiteley AT, Garelis NE, Peterson BN, et al. c-di-AMP modulates Listeria monocytogenes central metabolism to regulate growth, antibiotic resistance and osmoregulation[J]. Mol Microbiol, 2017, 104(2): 212-233.
[12] Corrigan RM, Abbott JC, Burhenne H, et al. c-di-AMP is a new second messenger in Staphylococcus aureus with a role in controlling cell size and enve-lope stress[J]. PLoS Pathog, 2011, 7(9):e1002217.
[13] Kamegaya T, Kuroda K, Hayakawa Y. Identification of a Streptococcus pyogenes SF370 gene involved in production of c-di-AMP[J]. Nagoya J Med Sci, 2011, 73(1/2):49-57.
[14] Bai Y, Yang J, Zhou X, et al. Mycobacterium tube-rculosis Rv3586(DacA) is a diadenylate cyclase that converts ATP or ADP into c-di-AMP[J]. PLoS One, 2012, 7(4):e35206.
[15] Yang J, Bai Y, Zhang Y, et al. Deletion of the cyclic di-AMP phosphodiesterase gene(cnpB) in Mycobac-terium tuberculosis leads to reduced virulence in a mouse model of infection[J]. Mol Microbiol, 2014, 93(1):65-79.
[16] Smith WM, Pham TH, Lei L, et al. Heat resistance and salt hypersensitivity in Lactococcus lactis due to spontaneous mutation of llmg_1816(gdpP) induced by high-temperature growth[J]. Appl Environ Micro-biol, 2012, 78(21):7753-7759.
[17] Ye M, Zhang JJ, Fang X, et al. DhhP, a cyclic di-AMP phosphodiesterase of Borrelia burgdorferi , is essential for cell growth and virulence[J]. Infect Im-mun, 2014, 82(5):1840-1849.
[18] Jervis AJ, Thackray PD, Houston CW, et al. SigM-responsive genes of Bacillus subtilis and their pro-moters[J]. J Bacteriol, 2007, 189(12):4534-4538.
[19] Cao M, Kobel PA, Morshedi MM, et al. Defining the Bacillus subtilis sigma(W) regulon: a comparative analysis of promoter consensus search, run-off transcription/macroarray analysis(ROMA), and transcriptional profiling approaches[J]. J Mol Biol, 2002, 316(3):443-457.
[20] Mehne FM, Gunka K, Eilers H, et al. Cyclic di-AMP homeostasis in Bacillus subtilis : both lack and high level accumulation of the nucleotide are detrimental for cell growth[J]. J Biol Chem, 2013, 288(3):2004- 2017.
[21] Burhenne H, Kaever V. Quantification of cyclic dinucleotides by reversed-phase LC-MS/MS[J]. Me-thods Mol Biol, 2013, 1016:27-37.
[22] Zheng C, Wang J, Luo Y, et al. Highly efficient enzymatic preparation of c-di-AMP using the dia-denylate cyclase DisA from Bacillus thuringiensis [J]. Enzyme Microb Technol, 2013, 52(6/7):319-324.
[23] Rao F, See RY, Zhang D, et al. YybT is a signaling protein that contains a cyclic dinucleotide phospho-diesterase domain and a GGDEF domain with ATPase activity[J]. J Biol Chem, 2010, 285(1):473-482.
[24] Tan E, Rao F, Pasunooti S, et al. Solution structure of the PAS domain of a thermophilic YybT protein homolog reveals a potential ligand-binding site[J]. J Biol Chem, 2013, 288(17):11949-11959.
[25] Zhang L, Li W, He ZG. DarR, a TetR-like transcrip-tional factor, is a cyclic di-AMP-responsive repressor in Mycobacterium smegmatis [J]. J Biol Chem, 2013, 288(5):3085-3096.
[26] Corrigan RM, Campeotto I, Jeganathan T, et al. Systematic identification of conserved bacterial c-di-AMP receptor proteins[J]. Proc Natl Acad Sci U S A, 2013, 110(22):9084-9089.
[27] Epstein W. The roles and regulation of potassium in bacteria[J]. Prog Nucleic Acid Res Mol Biol, 2003, 7:293-320.
[28] Müller M, Hopfner KP, Witte G. c-di-AMP reco-gnition by Staphylococcus aureus PstA[J]. FEBS Lett, 2015, 589(1):45-51.
[29] Ninfa AJ, Atkinson MR. PⅡ signal transduction proteins[J]. Trends Microbiol, 2000, 8(4):172-179.
[30] Boye E. DisA, a busy bee that monitors chromosome integrity[J]. Cell, 2006, 125(4):641-643.
[31] Eiamphungporn W, Helmann JD. The Bacillus sub - tilis sigma (M) regulon and its contribution to cell envelope stress responses[J]. Mol Microbiol, 2008, 67(4):830-848.
[32] Wang X, Davlieva M, Reyes J, et al. A novel pho-sphodiesterase of the GdpP family modulates cyclic di-AMP levels in response to cell membrane stress in daptomycin-resistant enterococci[J]. Antimicrob Agents Chemother, 2017, 61(3):e01422-16.
[33] Gries CM, Bruger EL, Moormeier DE, et al. Cyclic di-AMP released from Staphylococcus aureus biofilm induces a macrophage typeⅠinterferon response[J]. Infect Immun, 2016, 84(12):3564-3574.
[34] Gundlach J, Rath H, Herzberg C, et al. Second mes-senger signaling in Bacillus subtilis : accumulation of cyclic di-AMP inhibits biofilm formation[J]. Front Microbiol, 2016, 7:804.
[35] Thibessard A, Borges F, Fernandez A, et al. Identi-fication of Streptococcus thermophilus CNRZ368 genes involved in defense against superoxide stress [J]. Appl Environ Microbiol, 2004, 70(4):2220-2229.
[36] Bowman L, Zeden MS, Schuster CF, et al. New insights into the cyclic di-adenosine monophosphate (c-di-AMP) degradation pathway and the require-ment of the cyclic dinucleotide for acid stress resis-tance in Staphylococcus aureus [J]. J Biol Chem, 2016, 291(53):26970-26986.
[37] Cheng X, Zheng X, Zhou X, et al. Regulation of oxidative response and extracellular polysaccharide synthesis by a diadenylate cyclase in Streptococcus mutans [J]. Environ Microbiol, 2016, 18(3):904-922.
[38] Peng X, Zhang Y, Bai G, et al. Cyclic di-AMP me-diates biofilm formation[J]. Mol Microbiol, 2016, 99(5):945-959.
[39] 邱伟, 程兴群, 周学东, 等. 牙龈卟啉单胞菌c-di-AMP代谢相关基因的克隆及表达纯化[J]. 华西口腔医学杂志, 2015, 33(6):607-612.
Qiu W, Cheng XQ, Zhou XD, et al. Cloning, expres-sion, and purification of c-di-AMP metabolism-related genes from Porphyromonas gingivalis [J].West Chin J Stomatol, 2015, 33(6):607-612.
[1] 王冠儒,冯强. 牙龈卟啉单胞菌在阿尔兹海默症发生中作用的研究进展[J]. 国际口腔医学杂志, 2022, 49(4): 397-403.
[2] 郑直, 颜世果. 疱疹病毒与牙周炎的关系[J]. 国际口腔医学杂志, 2018, 45(2): 224-227.
[3] 刘琨,侯本祥. 粪肠球菌和变异链球菌脂磷壁酸的生物学活性[J]. 国际口腔医学杂志, 2017, 44(1): 118-124.
[4] 周双双 郑欣 周学东 徐欣. 菌斑生物膜产碱代谢与龋病[J]. 国际口腔医学杂志, 2016, 43(5): 573-577.
[5] 程远 殷艳丽 赵蕾. 龈沟产线菌的研究进展[J]. 国际口腔医学杂志, 2014, 41(5): 593-597.
[6] 郭强1，2 徐欣1 周学东1. 口腔细菌代谢产碱及其分子生物学研究进展[J]. 国际口腔医学杂志, 2013, 40(1): 80-85.
[7] 朱赟婕综述 陈晖审校. 牙龈卟啉单胞菌与冠心病之间的关系[J]. 国际口腔医学杂志, 2012, 39(6): 782-785.
[8] 袁艺 郭强 李明云 熊萍 李继遥 朱硃 李燕 龚其美 肖晓蓉 肖丽英. 链球菌和放线菌的胞外代谢物代谢组学鉴定[J]. 国际口腔医学杂志, 2011, 38(4): 399-402.
[9] 栾晓玲综述 王艳 冯希平审校. 口腔细菌尿素酶的检测[J]. 国际口腔医学杂志, 2011, 38(3): 358-360.
[10] 陈婷综述 吴补领审校. 口腔细菌的新种属及其生物学特性[J]. 国际口腔医学杂志, 2011, 38(2): 181-184.
[11] 于西佼,李纾,. 报告基因及其在生物膜研究中的应用[J]. 国际口腔医学杂志, 2006, 33(01): 15-17.
[12] 李煌,李松,徐芸,陈扬熙. 蛋白质组学技术在细胞信号传递机制研究中的应用[J]. 国际口腔医学杂志, 2005, 32(05): 344-346.
[13] 高燕,刘丽. α6β4整合素在上皮移行中的作用[J]. 国际口腔医学杂志, 2004, 31(05): 340-342.
[14] 李孝权. 口腔细菌新种属及分类位置变动[J]. 国际口腔医学杂志, 2002, 29(06): -.
[15] 李艳红. 口腔细菌间相互作用研究进展[J]. 国际口腔医学杂志, 2002, 29(03): -.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] 张新春. 桩冠修复与无髓牙的保护[J]. 国际口腔医学杂志, 1999, 26(06): .
[2] 王昆润. 长期单侧鼻呼吸对头颅发育有不利影响[J]. 国际口腔医学杂志, 1999, 26(05): .
[3] 彭国光. 颈淋巴清扫术中颈交感神经干的解剖变异[J]. 国际口腔医学杂志, 1999, 26(05): .
[4] 杨凯. 淋巴化疗的药物运载系统及其应用现状[J]. 国际口腔医学杂志, 1999, 26(05): .
[5] 康非吾. 种植义齿下部结构生物力学研究进展[J]. 国际口腔医学杂志, 1999, 26(05): .
[6] 柴枫. 可摘局部义齿用Co-Cr合金的激光焊接[J]. 国际口腔医学杂志, 1999, 26(04): .
[7] 孟姝,吴亚菲,杨禾. 伴放线放线杆菌产生的细胞致死膨胀毒素及其与牙周病的关系[J]. 国际口腔医学杂志, 2005, 32(06): 458 -460 .
[8] 费晓露,丁一,徐屹. 牙周可疑致病菌对口腔黏膜上皮的粘附和侵入[J]. 国际口腔医学杂志, 2005, 32(06): 452 -454 .
[9] 赵兴福,黄晓晶. 变形链球菌蛋白组学研究进展[J]. 国际口腔医学杂志, 2008, 35(S1): .
[10] 庞莉苹,姚江武. 抛光和上釉对陶瓷表面粗糙度、挠曲强度及磨损性能的影响[J]. 国际口腔医学杂志, 2008, 35(S1): .