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表观遗传和蛋白质翻译后修饰在细菌耐药中的作用

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  • 西南大学生命科学学院,三峡库区生态环境与生物资源省部共建国家重点实验室培育基地,现代生物医药研究所,重庆 400715
谢龙祥,博士研究生,专业方向:药用微生物功能基因组学与新药筛选模型。E-mail: xielongxiang123@126.com

收稿日期: 2015-03-01

  修回日期: 2015-05-12

  网络出版日期: 2015-08-20

基金资助

国家自然科学基金(编号:81371851, 81071316, 81271882, 81301394), 教育部新世纪优秀人才资助计划(编号:NCET-11-0703), 国家传染病科技重大专项(编号:2008ZX10003-006, 2008ZX10003-001), 中央高校基本业务费(编号:XDJK2013D003,XDJK2014D040)和重庆市教委研究生创新项目(编号:CYS14044)资助

The roles of epigenetics and protein post-translational modifications in bacterial antibiotic resistance

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  • Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, School of Life Sciences, Southwest University, Chongqing 400715, China

Received date: 2015-03-01

  Revised date: 2015-05-12

  Online published: 2015-08-20

摘要

日益严重的细菌耐药性有可能使人类重回前抗生素时代。细菌的耐药机理多样,深入研究细菌的耐药性形成机理有助于开发控制耐药细菌感染的新措施。表观遗传和蛋白质翻译后修饰在细胞代谢、信号转导、蛋白质降解、调控DNA复制、应激反应等方面都具有重要作用。近年来研究表明表观遗传和蛋白质翻译后修饰在细菌耐药中也扮演着重要的角色。本文总结了DNA甲基化、调控型RNAs等表观遗传因素和磷酸化、琥珀酰基化等蛋白质翻译后修饰因素在细菌耐药性中的调控作用,以期为抗生素靶标选择和抗生素开发设计提供新 思路。

本文引用格式

谢龙祥, 于召箫, 郭思瑶, 李萍, AbualgasimElgailiAbdalla, 谢建平 . 表观遗传和蛋白质翻译后修饰在细菌耐药中的作用[J]. 遗传, 2015 , 37(8) : 793 -800 . DOI: 10.16288/j.yczz.15-092

Abstract

The increasing antibiotic resistance is now threatening to take us back to a pre-antibiotic era. Bacteria have evolved diverse resistance mechanisms, on which in-depth research could help the development of new strategies to control antibiotic-resistant infections. Epigenetic alterations and protein post-translational modifications (PTMs) play important roles in multiple cellular processes such as metabolism, signal transduction, protein degradation, DNA replication regulation and stress response. Recent studies demonstrated that epigenetics and PTMs also play vital roles in bacterial antibiotic resistance. In this review, we summarize the regulatory roles of epigenetic factors including DNA methylation and regulatory RNAs as well as PTMs such as phosphorylation and succinylation in bacterial antibiotic resistance, which may provide innovative perspectives on selecting antibacterial targets and developing antibiotics.

参考文献

[1] Sethi S, Murphy TF. Bacterial infection in chronic obstructive pulmonary disease in 2000: a state-of-the-art review. Clin Microbiol Rev , 2001, 14(2): 336-363.
[2] Blair JMA, Webber MA, Baylay AJ, Ogbolu DO, Piddock LVJ. Molecular mechanisms of antibiotic resistance. Nat Rev Microbiol , 2015, 13(1): 42-51.
[3] Hampton T. Report reveals scope of US antibiotic resistance threat. JAMA , 2013, 310(16): 1661-1663.
[4] Walsh CT, Garneau-Tsodikova S, Gatto JG Jr. Protein posttranslational modifications: the chemistry of proteome diversifications. Angew Chem Int Ed , 2005, 44(45): 7342-7372.
[5] Tsuchido T, Takano M. Sensitization by heat treatment of Escherichia coli K-12 cells to hydrophobic antibacterial compounds. Antimicrob Agents Chemother , 1988, 32(11): 1680-1683.
[6] Jackson LA, Pan JC, Day MW, Dyer DW. Control of RNA stability by NrrF, an iron-regulated small RNA in Neisseria gonorrhoeae . J Bacteriol, 2013, 195(22): 5166-5173.
[7] Chuanchuen R, Karkhoff-Schweizer RR, Schweizer HP. High-level triclosan resistance in Pseudomonas aeruginosa is solely a result of efflux. Am J Infect Control , 2003, 31(2): 124-127.
[8] Vranakis I, Goniotakis I, Psaroulaki A, Sandalakis V, Tselentis Y, Gevaert K, Tsiotis G. Proteome studies of bacterial antibiotic resistance mechanisms. J Proteomics , 2014, 97: 88-99.
[9] Mc Dermott PF, Walker RD, White DG. Antimicrobials: modes of action and mechanisms of resistance. Int J Toxicol , 2003, 22(2): 135-143.
[10] Bradford PA. Extended-spectrum β-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clin Microbiol Rev , 2001, 14(4): 933-951.
[11] Collier J. Epigenetic regulation of the bacterial cell cycle. Curr Opin Microbiol , 2009, 12(6): 722-729.
[12] Heusipp G, Fälker S, Schmidt MA. DNA adenine methylation and bacterial pathogenesis. Int J Med Microbiol , 2007, 297(1): 1-7.
[13] Low DA, Weyand NJ, Mahan MJ. Roles of DNA adenine methylation in regulating bacterial gene expression and virulence. Infect Immun , 2001, 69(12): 7197-7204.
[14] Militello KT, Mandarano AH, Varechtchouk O, Simon RD. Cytosine DNA methylation influences drug resistance in Escherichia coli through increased sugE expression. FEMS Microbiol Lett , 2014, 350(1): 100-106.
[15] Srikhanta YN, Maguire TL, Stacey KJ, Grimmond SM, Jennings MP. The phasevarion: a genetic system controlling coordinated, random switching of expression of multiple genes. Proc Natl Acad Sci USA , 2005, 102(15): 5547-5551.
[16] Srikhanta YN, Fox KL, Jennings MP. The phasevarion: phase variation of type III DNA methyltransferases controls coordinated switching in multiple genes. Nat Rev Microbiol , 2010, 8(3): 196-206.
[17] Seib KL, Pigozzi E, Muzzi A, Gawthorne JA, Delany I, Jennings MP, Rappuoli R. A novel epigenetic regulator associated with the hypervirulent Neisseria meningitidis clonal complex 41/44. FASEB J , 2011, 25(10): 3622-3633.
[18] Srikhanta YN, Dowideit SJ, Edwards JL, Falsetta ML, Wu HJ, Harrison OB, Fox KL, Seib KL, Maguire TL, Wang AHJ, Maiden MC, Grimmond SM, Apicella MA, Jennings MP. Phasevarions mediate random switching of gene expression in pathogenic Neisseria . PLoS Pathog , 2009, 5(4): e1000400.
[19] Jen FEC, Seib KL, Jennings MP. Phasevarions mediate epigenetic regulation of antimicrobial susceptibility in Neisseria meningitidis . Antimicrob Agents Chemother , 2014, 58(7): 4219-4221.
[20] Okamoto S, Tamaru A, Nakajima C, Nishimura K, Tanaka Y, Tokuyama S, Suzuki Y, Ochi K. Loss of a conserved 7-methylguanosine modification in 16S rRNA confers low-level streptomycin resistance in bacteria. Mol Microbiol , 2007, 63(4): 1096-1106.
[21] Nishimura K, Johansen SK, Inaoka T, Hosaka T, Tokuyama S, Tahara Y, Okamoto S, Kawamura F, Douthwaite S, Ochi K. Identification of the RsmG methyltransferase target as 16S rRNA nucleotide G527 and characterization of Bacillus subtilis r
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