期刊文献+

结核分枝杆菌耐氟喹诺酮类药物的分子机制研究进展 被引量:9

Mechanisms of fluoroquinolone resistance in Mycobacterium tuberculosis
下载PDF
导出
摘要 结核病是由结核分枝杆菌(Mycobacterium tuberculosis)通过空气传播引起人类感染的慢性传染病,耐药结核分枝杆菌的流行是目前结核病防治的世界难题。氟喹诺酮类药物是人工合成药物,应用于耐药结核的临床治疗中,在治疗中起着核心的作用。但近年来,氟喹诺酮类药物的抗性菌株不断出现,愈发增加了结核病治疗的困难与治疗失败风险。在临床中氟喹诺酮药物的靶点比较清楚,是结核分枝杆菌的DNA旋转酶。目前发现结核分枝杆菌耐氟喹诺酮类药物的机制主要包括药物靶点DNA旋转酶的关键氨基酸改变、药物外排泵系统、细菌细胞壁厚度的增加以及喹诺酮抗性蛋白Mfp A介导的DNA旋转酶活性调控。其中在氟喹诺酮靶标DNA旋转酶功能活性改变的耐药机制方面,编码DNA旋转酶基因突变一直是研究的热点,但近年来发现DNA旋转酶的调控蛋白Mfp A以及DNA旋转酶的修饰在细菌耐药性中起着重要的作用,相关机制还亟待发现。本文综述了当前结核分枝杆菌耐氟喹诺酮类药物的作用机制,旨在为研发精准诊断技术和药物发掘提供科学理论基础和参考。 Tuberculosis, caused by the pathogen Mycobacterium tuberculosis, is one of the world's deadliest bacterial infectious disease. It is still a global-health threat, particularly because of the drug-resistant forms. Fluoroquinolones, with target of gyrase, are among the drugs used to treat tuberculosis. However, their widespread use has led to bacterial resistance. The molecular mechanisms of fluoroquinolone resistance in mycobacterium tuberculosis have been reported, such as DNA gyrase mutations, drug efflux pumps system, bacterial cell wall thickness and pentapeptide proteins(Mfp A) mediated regulation of gyrase. Mutations in gyrase conferring quinolone resistance play important roles and have been extensively studied. Recent studies have shown that the regulation of DNA gyrase affects mycobacterial drug resistance, but the mechanisms, especially by post-translational modification and regulatory proteins, are poorly understood. In this review, we summarize the fluoroquinolone drug development, and the molecular genetics of fluoroquinolone resistance in mycobacteria. Comprehensive understanding of the mechanisms of fluoroquinolone resistance in Mycobacterium tuberculosis will open a new view on understanding drug resistance in mycobacteria and lead to novel strategies to develop new accurate diagnosis methods.
作者 张玉娇 李晓静 米凯霞 Yujiao Zhang Xiaojing Li Kaixia Mi(CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences Beijing 100101, China)
出处 《遗传》 CAS CSCD 北大核心 2016年第10期918-927,共10页 Hereditas(Beijing)
基金 国家自然科学基金项目(编号:31270178,31670137)资助~~
关键词 结核分枝杆菌 氟喹诺酮 耐药 DNA旋转酶 Mycobacterium tuberculosis fluoroquinolone drug-resistance DNA gyrase
  • 相关文献

参考文献59

  • 1Ginsburg AS, Grosset JH, Bishai WR. Fluoroquinolones, tuberculosis, and resistance. Lancet Infect Dis, 2003, 3(7): 432-442.
  • 2Gandhi NR, Nunn P, Dheda K, Schaaf HS, Zignol M, van Soolingen D, Jensen P, Bayona J. Multidrug-resistant and extensively drug-resistant tuberculosis: a threat to global con- trol of tuberculosis. Lancet, 2010, 375(9728): 1830-1843.
  • 3Manjelievskaia J, Erck D, Piracha S, Schrager L. Drug- resistant TB: deadly, costly and in need of a vaccine. Trans Roy Soc Trop Med Hyg, 2016, 110(3): 186-191.
  • 4Marks SM, Flood J, Seaworth B, Hirsch-Moverman Y, Armstrong L, Mase S, Salcedo K, Oh P, Graviss EA, Col- son PW, Armitige L, Revuelta M, Sheeran K. Treatment practices, outcomes, and costs of multidrug-resistant and extensively drug-resistant tuberculosis, United States, 2005-2007. Emerg Infect Dis, 2014, 20(5): 812-821.
  • 5O'Donnell MR, Jarand J, Loveday M, Padayatchi N, Zel- nick J, Werner L, Naidoo K, Master I, Osburn G, Kvas- novsky C, Shean K, Pai M, Van der Walt M, Horsburgh CR, Dheda K. High incidence of hospital admissions with multidrug-resistant and extensively drug-resistant tuber- culosis among South African health care workers. Ann In- tern Med, 2010, 153(8): 516-522.
  • 6Nuermberger E, Tyagi S, Tasneen R, Williams KN, Al- meida D, Rosenthal I, Grosset JH. Powerful bactericidal and sterilizing activity of a regimen containing PA-824, moxifloxacin, and pyrazinamide in a murine model of tu- berculosis. Antimicrob Agents Chemother, 2008, 52(4): 1522-1524.
  • 7Veziris N, Ibrahim M, Lotmis N, Andries K, Jarlier V. Steri- lizing activity of second-line regimens containing TMC207 in a murine model of tuberculosis. PLoS One, 2011, 6(3): e17556.
  • 8Takiff H, Guerrero E. Current prospects for the fluoro- quinolones as first-line tuberculosis therapy. Antimicrob Agents Chemother, 2011, 55(12): 5421-5429.
  • 9An DD, Duyen NTH, Lan NTN, Hoa DV, Ha DTM, Kiet VS, Thu DDA, Van Vinh Chau N, Dung NH, Sy DN, Far- rar J, Caws M. Beijing genotype of Mycobacterium tu- berculosis is significantly associated with high-level flu- oroquinolone resistance in Vietnam. Antimicrob Agents Chemother, 2009, 53(11): 4835-4839.
  • 10Sun ZG, Zhang JY, Zhang XX, Wang SM, Zhang Y, Li CY. Comparison of gyrA gene mutations between laborato- ry-selected ofloxacin-resistant Mycobacterium tuberculo- sis strains and clinical isolates. Int J Antimicrob Agents, 2008, 31(2): 115-121.

二级参考文献12

  • 1Banerjee D, Mayer-Kuckuk P, Capiaux G, Budak-Alpdogan T,Gorlick R, Bertino J R. Novel aspects of resistance to drugs targeted to dihydrofolate reductase and thymidilate synthase. Biochim Biophys Acta, 2002, 1587(2-3): 164-173.
  • 2Suzuki T, Nishio K, Tanabe S. The MRP family and anticancer drug metabolism. Curr Drug Metab, 2001, 2(4): 367-377.
  • 3Gorlick R, Goker E, Trippett T, Waltham M, Banerjee D, Bertino J R. Intrinsic and acquired resistance to methotrexate in acute leukemia. N Engl J Med, 1996, 335(14): 1041-1048.
  • 4Calatozzolo C, Gelati M, Ciusani E, Sciacca F L, Pollo B, Cajola L, Marras C, Silvani A, Vitellaro-Zuccarello L, Croci D, BoiardiA, Salmaggi A. Expression of drug resistance proteins Pgp,MRP1, MRP3, MRP5 and GST-pi in human glioma. J Neurooncol, 2005, 74(2): 113-121.
  • 5Ruiz J C, Choi K H, von Hoff D D, Roninson I B, Wahl G M.Autonomously replicating episomes contain mdrl genes in a multidrug-resistant human cell line. Mol Cell Biol, 1989, 9(1):109-115.
  • 6Cole S P, Sparks K E, Fraser K, Loe D W, Grant C E, Wilson G M, Deeley R G.Pharmacological characterization of multidrug resistant MRP-transfected human tumor cells.Cancer Res, 1994,54(22): 5902-5910.
  • 7Ritter C A, Jedlitschky G, Meyer zu Schwabedissen H, Grube M,Kock K, Kroemer H K. Cellular export of drugs and signaling molecules by the ATP-binding cassette transporters MRP4 (ABCC4) and MRP5 (ABCC5). Drug Metab Rev, 2005, 37(1):253-278.
  • 8Zeng H, Chen Z S, Belinsky M G, Rea P A, Kruh G D. Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRPI: Effect of polyglutamylation on MTX transport. Cancer Res, 2001, 61 ( 19): 7225 -7232.
  • 9Hooijberg J H, Broxterman H J, Kool M, Assaraf Y G, Peters G J,Noordhuis P, Scheper R J, Borst P, Pinedo H M, Jansen G. Antifolate resistance mediated by the multidrug resistance protein MRP1 and MRP2. Cancer Res, 1999, 59(11): 2532-2535.
  • 10Sampath J, Adachi M, Hatse S, Naesens L, Balzarini J, Flatley R,Matherly L, Schuetzl J. Role of MRP4 and MRP5 in biology and Chemotherapy. AAPS Pharm Sci, 2002, 4 (3): 214-222.

共引文献8

同被引文献98

引证文献9

二级引证文献40

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部