氨基糖苷类抗生素的耐药机制研究进展
|
摘要
氨基糖苷类抗生素(AG)是高效的广谱抗生素,用于治疗许多革兰阴性菌和一些革兰阳性菌感染,随着临床的广泛应用,细菌的耐药性日趋严重。本文主要从核糖体修饰作用、氨基糖苷类抗生素的修饰酶的作用、药物的外排泵系统等方面对AGs的耐药机制进行阐述,为能合理使用AGs、控制细菌耐药性蔓延以及新型AG药物的开发提供参考。
Aminoglycoside antibiotics(AGs) are highly effective broad-spectrum antibiotics for the treatment of many Gram-negative bacteria and some Gram-positive bacteria. As antibiotics are widely used clinically, bacterial resistance is becoming more and more serious. This paper mainly describes the mechanisms of resistance to AGs in terms of ribosome modification, modification of AG-modifying enzymes and drug efflux pump system, which provides a reference for rational using of AGs to control the spread of antibiotic resistance in bacteria.
Aminoglycoside antibiotics(AGs) are highly effective broad-spectrum antibiotics for the treatment of many Gram-negative bacteria and some Gram-positive bacteria. As antibiotics are widely used clinically, bacterial resistance is becoming more and more serious. This paper mainly describes the mechanisms of resistance to AGs in terms of ribosome modification, modification of AG-modifying enzymes and drug efflux pump system, which provides a reference for rational using of AGs to control the spread of antibiotic resistance in bacteria.
引文
[1]Waksman S A.Antibiotic substances,production by microorganisms-nature and mode of action[J].Am J Public Health Nations Health,1944,34(4):358.
[2]O'Shea R,Moser H E.Physicochemical properties of antibacterial compounds:Implications for drug discovery[J].J Med Chem,2008,51(10):2871-2878.
[3]Becker B,Cooper M A.Aminoglycoside antibiotics in the21st century[J].ACS Chem Biol,2013,8(1):105-115.
[4]李明阳,李勇,王昉彤,等.氨基糖苷类抗生素肾毒性及生物标志物的研究进展[J].中国抗生素杂志,2014,39(2):85-88.
[5]Blair J M,Webber M A,Baylay A J,et al.Molecular mechanisms of antibiotic resistance[J].Nat Rev Microbiol,2015,13(1):42-51.
[6]Fernández L,Breidenstein E B M,Hancock R E W.Creeping baselines and adaptive resistance to antibiotics[J].Drug Resist Updat,2011,14(1):1-21.
[7]van Hoek A H,Mevius D,Guerra B,et al.Acquired antibiotic resistance genes:An overview[J].Front Microbiol,2012,3(2):384.
[8]Kobayashi Y,Akiyama Y,Murakami T,et al.Aminoglycoside antibiotics:US,9260465[P].2016-02-16.
[9]王雪玉.利用糖芯片技术检测氨基糖苷类抗生素与RNAs和蛋白质之间的相互作用[D].无锡:江南大学,2016.
[10]Schroeder R,Waldsich C,Wank H.Modulation of RNAfunction by aminoglycoside antibiotics[J].EMBO J,2000,19(1):1-9.
[11]Wasserman M R,Pulk A,Zhou Z,et al.Chemically related4,5-linked aminoglycoside antibiotics drive subunit rotation in opposite directions[J].Nat Commun,2015,6:7896.
[12]Magnet S,Blanchard J.Molecular insights into aminoglycoside action and resistance[J].Cheminform,2005,105(2):477-498.
[13]Maus C E,Plikaytis B B,Shinnick T M.Molecular analysis of cross-resistance to capreomycin,kanamycin,amikacin,and viomycin in Mycobacterium tuberculosis[J].Antimicrob Agents Chemother,2005,49(8):3192-3197.
[14]Georghiou S B,Magana M,Garfein R S,et al.Evaluation of genetic mutations associated with Mycobacterium tuberculosis resistance toamikacin,kanamycin and capreomycin:Asystematic review[J].Plos One,2012,7(3):e33275.
[15]费秋萍,张顺,蔡挺,等.外源性16s rRNA甲基化酶研究进展[J].中华医院感染学杂志,2016,26(7):1674-1676.
[16]Wachino J,Arakawa Y.Exogenously acquired 16S rRNAmethyltransferases found in aminoglycoside-resistant pathogenic Gram-negative bacteria:An update[J].Drug Resist Updat,2012,15(3):133-148.
[17]Gutierrez B,Douthwaite S,Gonzalezzorn B.Indigenous and acquired modifications in the aminoglycoside binding sites of Pseudomonas aeruginosa rRNAs[J].Rna Biol,2013,10(8):1324-1332.
[18]Gutierrez B,Escudero J A,San M A,et al.Fitness cost and interference of Arm/Rmt aminoglycoside resistance with the RsmF housekeeping methyltransferases[J].Antimicrob Agents Chemother,2012,56(5):2335-2341.
[19]Ramirez M S,Tolmasky M E.Aminoglycoside modifying enzymes[J].Drug Resist Updat,2010,13(6):151-171.
[20]武灵芝,胡栋,秦猛.氨基糖苷类修饰酶引起的细菌耐药性机制的研究进展[J].生物物理学报,2013,29(1):15-25.
[21]李聪然,游雪甫,蒋建东.氨基糖苷类双功能修饰酶AAC(6')-APH(2'')的研究进展[J].中国感染与化疗杂志,2007,7(6):468-471.
[22]Reeves A Z,Campbell P J,Sultana R,et al.Aminoglycoside cross-resistance in Mycobacterium tuberculosis due to mutations in the 5'untranslated region of whiB7[J].Antimicrob Agents Chemother,2013,57:1857-1865.
[23]Cox G,Stogios P J,Savchenko A,et al.Structural and molecular basis for resistance to aminoglycoside antibiotics by the adenylyltransferase ANT(2'')-Ia[J].Mbio,2015,6(1):e02180-14.
[24]Li Y,Green K D,Johnson B R,et al.Inhibition of aminoglycoside acetyltransferase resistance enzymes by metal salts[J].Antimicrob Agents Chemother,2015,59(7):4148-4156.
[25]Maianti J P,Kanazawa H,Dozzo P,et al.Toxicity modulation,resistance enzyme evasion,and A-site X-ray structure of broad-spectrum antibacterial neomycin analogs[J].Acs Chem Biol,2014,9(9):2067-2073.
[26]Li X Z,Plésiat P,Nikaido H.The Challenge of effluxmediated antibiotic resistance in Gram-negative bacteria[J].CMR,2015,28(2):337-418.
[27]Fernández L,Gooderham W J,Bains M,et al.Adaptive resistance to the"Last Hope"antibiotics polymyxin B and colistin in Pseudomonas aeruginosa is mediated by the novel two-component regulatory system ParR-ParS[J].Antimicrob Agents Chemother,2010,54(8):3372-3382.
[28]Dong H K,Lu C D.Polyamines induce resistance to cationic peptide,aminoglycoside,and quinolone antibiotics in Pseudomonas aeruginosa PAO1[J].Antimicrob Agents Chemother,2006,50(5):1615-1622.
[29]Agafitei O,Kim E J,MAGuire T,et al.The role of Escherichia coli porins OmpC and OmpF in antibiotic cross resistance induced by sub-inhibitory concentrations of kanamycin[J].JEMI,2010,14:34-39.
[30]Fernández L,Hancock R E W.Adaptive and mutational resistance:Role of porins and efflux pumps in drug resistance[J].CMR,2012,25(4):661-681.
[31]杨祚明,谭孟源,符春花,等.多重耐药铜绿假单胞菌外排泵基因表达与耐药表型和耐药程度的关系[J].中华实用诊断与治疗杂志,2016,30(1):86-88.
[32]TBrake L H M T,Knegt G J D,Steenwinkel J E D,et al.The role of efflux pumps in tuberculosis treatment and their promise as a target in drug development:Unraveling the black box[J].Annu Rev Pharmacool Toxicol,2018,58(1):271-291.
[33]Hinz A,Lee S,Jacoby K,et al.Membrane proteases and aminoglycoside antibiotic resistance[J].J Bacteriol,2011,193(18):4790-4797.
[34]Kindrachuk K N,Fernández L,Bains M,et al.Involvement of an ATP-dependent protease,PA0779/AsrA,in inducing heat shock in response to tobramycin in Pseudomonas aeruginosa[J].Antimicrob Agents Chemother,2011,55(5):1874-1882.
[35]Lau CH,Hughes D,Poole K.MexY-promoted aminoglycoside resistance in Pseudomonas aeruginosa:Involvement of a putative proximal binding pocket in aminoglycoside recognition[J].Mbio,2014,5(2):e01068.
[36]Almaghrabi R,Clancy C J,Doi Y,et al.Carbapenemresistant Klebsiella pneumoniae strains exhibit diversity in aminoglycoside-modifying enzymes,which exert differing effects on plazomicin and other agents[J].Antimicrob Agents Chemother,2014,58(8):4443-4451.
[37]Garcíasalguero C,Rodríguezavial I,Picazo J J,et al.Can plazomicin alone or in combination be a therapeutic option against carbapenem-resistant Acinetobacter baumannii[J].Antimicrob Agents Chemother,2015,59(10):5959-5966.
[2]O'Shea R,Moser H E.Physicochemical properties of antibacterial compounds:Implications for drug discovery[J].J Med Chem,2008,51(10):2871-2878.
[3]Becker B,Cooper M A.Aminoglycoside antibiotics in the21st century[J].ACS Chem Biol,2013,8(1):105-115.
[4]李明阳,李勇,王昉彤,等.氨基糖苷类抗生素肾毒性及生物标志物的研究进展[J].中国抗生素杂志,2014,39(2):85-88.
[5]Blair J M,Webber M A,Baylay A J,et al.Molecular mechanisms of antibiotic resistance[J].Nat Rev Microbiol,2015,13(1):42-51.
[6]Fernández L,Breidenstein E B M,Hancock R E W.Creeping baselines and adaptive resistance to antibiotics[J].Drug Resist Updat,2011,14(1):1-21.
[7]van Hoek A H,Mevius D,Guerra B,et al.Acquired antibiotic resistance genes:An overview[J].Front Microbiol,2012,3(2):384.
[8]Kobayashi Y,Akiyama Y,Murakami T,et al.Aminoglycoside antibiotics:US,9260465[P].2016-02-16.
[9]王雪玉.利用糖芯片技术检测氨基糖苷类抗生素与RNAs和蛋白质之间的相互作用[D].无锡:江南大学,2016.
[10]Schroeder R,Waldsich C,Wank H.Modulation of RNAfunction by aminoglycoside antibiotics[J].EMBO J,2000,19(1):1-9.
[11]Wasserman M R,Pulk A,Zhou Z,et al.Chemically related4,5-linked aminoglycoside antibiotics drive subunit rotation in opposite directions[J].Nat Commun,2015,6:7896.
[12]Magnet S,Blanchard J.Molecular insights into aminoglycoside action and resistance[J].Cheminform,2005,105(2):477-498.
[13]Maus C E,Plikaytis B B,Shinnick T M.Molecular analysis of cross-resistance to capreomycin,kanamycin,amikacin,and viomycin in Mycobacterium tuberculosis[J].Antimicrob Agents Chemother,2005,49(8):3192-3197.
[14]Georghiou S B,Magana M,Garfein R S,et al.Evaluation of genetic mutations associated with Mycobacterium tuberculosis resistance toamikacin,kanamycin and capreomycin:Asystematic review[J].Plos One,2012,7(3):e33275.
[15]费秋萍,张顺,蔡挺,等.外源性16s rRNA甲基化酶研究进展[J].中华医院感染学杂志,2016,26(7):1674-1676.
[16]Wachino J,Arakawa Y.Exogenously acquired 16S rRNAmethyltransferases found in aminoglycoside-resistant pathogenic Gram-negative bacteria:An update[J].Drug Resist Updat,2012,15(3):133-148.
[17]Gutierrez B,Douthwaite S,Gonzalezzorn B.Indigenous and acquired modifications in the aminoglycoside binding sites of Pseudomonas aeruginosa rRNAs[J].Rna Biol,2013,10(8):1324-1332.
[18]Gutierrez B,Escudero J A,San M A,et al.Fitness cost and interference of Arm/Rmt aminoglycoside resistance with the RsmF housekeeping methyltransferases[J].Antimicrob Agents Chemother,2012,56(5):2335-2341.
[19]Ramirez M S,Tolmasky M E.Aminoglycoside modifying enzymes[J].Drug Resist Updat,2010,13(6):151-171.
[20]武灵芝,胡栋,秦猛.氨基糖苷类修饰酶引起的细菌耐药性机制的研究进展[J].生物物理学报,2013,29(1):15-25.
[21]李聪然,游雪甫,蒋建东.氨基糖苷类双功能修饰酶AAC(6')-APH(2'')的研究进展[J].中国感染与化疗杂志,2007,7(6):468-471.
[22]Reeves A Z,Campbell P J,Sultana R,et al.Aminoglycoside cross-resistance in Mycobacterium tuberculosis due to mutations in the 5'untranslated region of whiB7[J].Antimicrob Agents Chemother,2013,57:1857-1865.
[23]Cox G,Stogios P J,Savchenko A,et al.Structural and molecular basis for resistance to aminoglycoside antibiotics by the adenylyltransferase ANT(2'')-Ia[J].Mbio,2015,6(1):e02180-14.
[24]Li Y,Green K D,Johnson B R,et al.Inhibition of aminoglycoside acetyltransferase resistance enzymes by metal salts[J].Antimicrob Agents Chemother,2015,59(7):4148-4156.
[25]Maianti J P,Kanazawa H,Dozzo P,et al.Toxicity modulation,resistance enzyme evasion,and A-site X-ray structure of broad-spectrum antibacterial neomycin analogs[J].Acs Chem Biol,2014,9(9):2067-2073.
[26]Li X Z,Plésiat P,Nikaido H.The Challenge of effluxmediated antibiotic resistance in Gram-negative bacteria[J].CMR,2015,28(2):337-418.
[27]Fernández L,Gooderham W J,Bains M,et al.Adaptive resistance to the"Last Hope"antibiotics polymyxin B and colistin in Pseudomonas aeruginosa is mediated by the novel two-component regulatory system ParR-ParS[J].Antimicrob Agents Chemother,2010,54(8):3372-3382.
[28]Dong H K,Lu C D.Polyamines induce resistance to cationic peptide,aminoglycoside,and quinolone antibiotics in Pseudomonas aeruginosa PAO1[J].Antimicrob Agents Chemother,2006,50(5):1615-1622.
[29]Agafitei O,Kim E J,MAGuire T,et al.The role of Escherichia coli porins OmpC and OmpF in antibiotic cross resistance induced by sub-inhibitory concentrations of kanamycin[J].JEMI,2010,14:34-39.
[30]Fernández L,Hancock R E W.Adaptive and mutational resistance:Role of porins and efflux pumps in drug resistance[J].CMR,2012,25(4):661-681.
[31]杨祚明,谭孟源,符春花,等.多重耐药铜绿假单胞菌外排泵基因表达与耐药表型和耐药程度的关系[J].中华实用诊断与治疗杂志,2016,30(1):86-88.
[32]TBrake L H M T,Knegt G J D,Steenwinkel J E D,et al.The role of efflux pumps in tuberculosis treatment and their promise as a target in drug development:Unraveling the black box[J].Annu Rev Pharmacool Toxicol,2018,58(1):271-291.
[33]Hinz A,Lee S,Jacoby K,et al.Membrane proteases and aminoglycoside antibiotic resistance[J].J Bacteriol,2011,193(18):4790-4797.
[34]Kindrachuk K N,Fernández L,Bains M,et al.Involvement of an ATP-dependent protease,PA0779/AsrA,in inducing heat shock in response to tobramycin in Pseudomonas aeruginosa[J].Antimicrob Agents Chemother,2011,55(5):1874-1882.
[35]Lau CH,Hughes D,Poole K.MexY-promoted aminoglycoside resistance in Pseudomonas aeruginosa:Involvement of a putative proximal binding pocket in aminoglycoside recognition[J].Mbio,2014,5(2):e01068.
[36]Almaghrabi R,Clancy C J,Doi Y,et al.Carbapenemresistant Klebsiella pneumoniae strains exhibit diversity in aminoglycoside-modifying enzymes,which exert differing effects on plazomicin and other agents[J].Antimicrob Agents Chemother,2014,58(8):4443-4451.
[37]Garcíasalguero C,Rodríguezavial I,Picazo J J,et al.Can plazomicin alone or in combination be a therapeutic option against carbapenem-resistant Acinetobacter baumannii[J].Antimicrob Agents Chemother,2015,59(10):5959-5966.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |