金属离子铁和锌对鲍曼不动杆菌的抗菌作用机制研究进展
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摘要
由于抗菌药物的开发周期越来越长,远远赶不上细菌耐药的发展速度,临床鲍曼不动杆菌多重耐药与泛耐药现象日益严重。因此,人们越来越关注对抗菌药物以外的抗菌物质的开发,尤其是从生存条件方面来研究抑制耐药菌活性的方法,如金、银、铜等金属离子对鲍曼不动杆菌的作用。本文主要综述铁、锌等金属离子及其螯合物对鲍曼不动杆菌的抗菌作用。铁、锌等金属离子通过与一系列酶的协同作用,调控外排泵或影响生物膜形成及其黏附性等来抑制细菌生长。此外,一些非必需金属如金、银、钯等对鲍曼不动杆菌也具有很强的毒性,有良好的抗菌和降低耐药率的效果,可作为医疗留置器械的抗菌涂层等来预防感染。
Because the pace of new antibiotic development could not match the development of bacterial drug resistance,the phenomenon of multidrug-resistance and pan-resistance of Acinetobacter baumannii(A.baumannii)in clinical treatment is becoming widespread.Therefore,more and more attentions have been paid to the development of antimicrobial substances other than classical antimicrobial agents,such as metal ions and chelates.The antimicrobial activity of iron and zinc against A.baumannii was reviewed in this paper.Iron,zinc and the other essential metal ions can inhibit bacterial growth by regulating efflux pumps or affecting biofilm formation and adhesion.In addition,metals such as gold,silver and palladium,also have strong antibacterial effects and can be used as antimicrobial coating for medical indwelling devices to prevent infections.
Because the pace of new antibiotic development could not match the development of bacterial drug resistance,the phenomenon of multidrug-resistance and pan-resistance of Acinetobacter baumannii(A.baumannii)in clinical treatment is becoming widespread.Therefore,more and more attentions have been paid to the development of antimicrobial substances other than classical antimicrobial agents,such as metal ions and chelates.The antimicrobial activity of iron and zinc against A.baumannii was reviewed in this paper.Iron,zinc and the other essential metal ions can inhibit bacterial growth by regulating efflux pumps or affecting biofilm formation and adhesion.In addition,metals such as gold,silver and palladium,also have strong antibacterial effects and can be used as antimicrobial coating for medical indwelling devices to prevent infections.
引文
[1] Towner KJ.Acinetobacter:an old friend,but a new enemy[J].J Hosp Infect,2009,73(4):355-363.
[2]刘娟娟.离子对大肠杆菌生长的影响以及大肠杆菌生物被膜的初步研究[D/OL].济南:山东中医药大学,2010.http://cdmd.cnki.com.cn/Article/CDMD-10441-1011049129.htm.
[3] Mortensen BL,Skaar EP.The contribution of nutrient metalacquisitionandmetabolismtoAcinetobacter baumannii survival within the host[J].Front Cell Infect Microbiol,2013,3:95.doi:10.3389/fcimb.2013.00095.
[4] Vaidya MY,McBain AJ,Butler JA,Banks CE,Whitehead KA.Antimicrobial efficacy and synergy of metal ions against Enterococcus faecium,Klebsiella pneumonia and Acinetobacter baumanniiinplanktonicandbiofilm phenotypes[J].Sci Rep,2017,7(1):5911.doi:10.1038/s41598-017-05976-9.
[5]郑淑华,穆小萍,黄瑞玉,卢春敏,王浩平.铁螯合剂和硝酸镓对碳青霉烯类耐药鲍曼不动杆菌生长的影响[J].广东医学,2016,37(4):489-491.
[6] Lemire JA,Harrison JJ,Turner RJ.Antimicrobial activity of metals:mechanisms,molecular targets and applications[J].Nat Rev Microbiol,2013,11(6):371-384.
[7]周赟,易竹君,阙克婷,张震,刘作金.铁离子通过ROS-乙酰化P53促进巨噬细胞M1型极化[J].第三军医大学学报,2018,40(1):45-52.
[8]张鹏云,刘马峰,程安春.细菌铁离子利用系统与宿主抗感染免疫[J].生命科学研究,2016,20(1):82-88.
[9] Eijkelkamp BA, Hassan KA,Paulsen IT,Brown MH.Investigation ofthehumanpathogenAcinetobacter baumannii under iron limiting conditions[J]. BMC Genomics,2011,12:126.doi:10.1186/1471-2164-12-126.
[10] Antunes LC,Imperi F,Towner KJ,Visca P.Genomeassisted identification of putative iron-utilization genes in Acinetobacter baumannii and their distribution among a genotypically diverse collection of clinical isolates[J].Res Microbiol,2011,162(3):279-284.
[11] Koster W.Cytoplasmic membrane iron permease systems in the bacterial cell envelope[J].Front Biosci,2005,10:462-477.
[12] Wandersman C,Delepelaire P.Bacterial iron sources:from siderophores to hemophores[J].Annu Rev Microbiol,2004,58:611-647.
[13] MiethkeM, MarahielMA. Siderophore-basediron acquisition and pathogen control[J].Microbiol Mol Biol Rev,2007,71(3):413-451.
[14] Koronakis V,Eswaran J,Hughes C.Structure and function of TolC:the bacterial exit duct for proteins and drugs[J].Annu Rev Biochem,2004,73:467-489.
[15] Catel-Ferreira M,Marti S,Guillon L,Jara L,Coadou G,Molle V,Bouffartigues E,Bou G,Shalk I,Jouenne T,Vila-Farrés X,DéE.The outer membrane porin OmpW of Acinetobacter baumannii is involved in iron uptake and colistin binding[J].FEBS Lett,2016,590(2):224-231.
[16] Modarresi F,Azizi O,Shakibaie MR,Motamedifar M,Valibeigi B,Mansouri S.Effect of iron on expression of efflux pump(adeABC)and quorum sensing(luxI,luxR)genes in clinical isolates of Acinetobacter baumannii[J].APMIS,2015,123(11):959-968.
[17] Cucarella C,Solano C,Valle J,Amorena B,Lasa I,Penadés JR.Bap,a Staphylococcus aureus surface protein involved in biofilm formation[J].J Bacteriol,2001,183(9):2888-2896.
[18] Belenky P,Ye JD,Porter CB,Cohen NR,Lobritz MA,Ferrante T,Jain S,Korry BJ,Schwarz EG,Walker GC,Collins JJ.Bactericidal antibiotics induce toxic metabolic perturbations that lead to cellular damage[J].Cell Rep,2015,13(5):968-980.
[19] Yeom J,Imlay JA,Park W.Iron homeostasis affects antibiotic-mediated cell death in Pseudomonas species[J].J Biol Chem,2010,285(29):22689-22695.
[20] Yeom J,Jeon CO, Madsen EL,Park W.FerredoxinNADP+reductase from Pseudomonas putida functions as a ferric reductase[J].J Bacteriol,2009,191(5):1472-1479.
[21]谢芳.铁过载诱导ROS生成对造血干祖细胞功能的影响[D/OL].天津:天津医科大学,2012.http://cdmd.cnki.com.cn/Article/CDMD-10062-1012497576.htm.
[22] Rajendran M.Quinones as photosensitizer for photodynamic therapy:ROS generation, mechanism and detection methods[J]. Photodiag Photodyn Ther, 2016, 13:175-187.
[23] Prasad AS.Discovery of human zinc deficiency:its impact on human health and disease[J].Adv Nutr,2013,4(2):176-190.
[24] Andreini C,Banci L,Bertini I,Rosato A.Zinc through the three domains of life[J].J Proteome Res,2006,5(11):3173-3178.
[25] Nairn BL,Lonergan ZR,Wang J,Braymer JJ,Zhang Y,Calcutt MW,Lisher JP,Gilston BA,Chazin WJ,de CrécyLagard V, Giedroc DP,Skaar EP. The response of Acinetobacter baumannii to zinc starvation[J].Cell Host Microbe,2016,19(6):826-836.
[26]张留辉.锌离子对肺炎链球菌影响的蛋白质组学研究[D/OL].广州:暨南大学,2010.http://cdmd.cnki.com.cn/Article/CDMD-10559-2010123802.htm.
[27] Lin DL,Tran T,Alam JY,Herron SR,Ramirez MS,TolmaskyME. Inhibitionofaminoglycoside6′-Nacetyltransferase type Ib by zinc:reversal of amikacin resistance in Acinetobacter baumannii and Escherichia coli by a zinc ionophore[J].Antimicrob Agents Chemother,2014,58(7):4238-4241.
[28] Hood MI,Mortensen BL,Moore JL,Zhang Y,Kehl-Fie TE,Sugitani N,Chazin WJ,Caprioli RM,Skaar EP.IdentificationofanAcinetobacterbaumanniizinc acquisition system that facilitates resistance to calprotectinmediated zinc sequestration[J].PLoS Pathog,2012,8(12):e1003068.
[29]王晓岚.金属离子的抗菌性能及其抗菌机理研究[D/OL].广州:华南理工大学,2015.http://cdmd.cnki.com.cn/Article/CDMD-10561-1015988065.htm.
[30] Brandtzaeg P,Gabrielsen TO,Dale I,Müller F,Steinbakk M,Fagerhol MK.The leucocyte protein L1(calprotectin):aputative nonspecific defence factor at epithelial surfaces[J].Adv Exp Med Biol,1995,371A:201-206.
[31] van Faassen H,Kuolee R,Harris G,Zhao X,Conlan JW,Chen W. Neutrophils play an important role in host resistance to respiratory infection with Acinetobacter baumannii in mice[J].Infect Immun,2007,75(12):5597-5608.
[32] Ghasemi F,Jalal R.Antimicrobial action of zinc oxide nanoparticles in combination with ciprofloxacin and ceftazidimeagainstmultidrug-resistantAcinetobacter baumannii[J].J Glob Antimicrob Resist,2016,6:118-122.
[33] Huang HI,Shih HY,Lee CM,Yang TC,Lay JJ,Lin YE.In vitro efficacy of copper and silver ions in eradicating Pseudomonas aeruginosa,Stenotrophomonas maltophilia and Acinetobacterbaumannii:implicationsforon-site disinfection for hospital infection control[J].Water Res,2008,42(1-2):73-80.
[34]lamborováI,ZajícováV,Karpí2kováJ,Exnar P,Stibor I.New type of protective hybrid and nanocomposite hybrid coatings containing silver and copper with an excellent antibacterial effect especially against MRSA[J].Mater Sci Eng C Mater Biol Appl,2013,33(1):265-273.
[35] de Moraes AC,Lima BA,de Faria AF,Brocchi M,Alves OL.Graphene oxide-silver nanocomposite as a promising biocidal agent against methicillin-resistant Staphylococcus aureus[J].Int J Nanomed,2015,10:6847-6861.
[36] Weber BS,Kinsella RL,Harding CM,Feldman MF.The secrets of Acinetobacter secretion[J].Trends Microbiol,2017,25(7):532-545.
[37] García-Quintanilla M,Pulido MR,López-Rojas R,Pachón J, McConnell MJ. Emerging therapies for multidrug resistant Acinetobacter baumannii[J].Trends Microbiol,2013,21(3):157-163.
[2]刘娟娟.离子对大肠杆菌生长的影响以及大肠杆菌生物被膜的初步研究[D/OL].济南:山东中医药大学,2010.http://cdmd.cnki.com.cn/Article/CDMD-10441-1011049129.htm.
[3] Mortensen BL,Skaar EP.The contribution of nutrient metalacquisitionandmetabolismtoAcinetobacter baumannii survival within the host[J].Front Cell Infect Microbiol,2013,3:95.doi:10.3389/fcimb.2013.00095.
[4] Vaidya MY,McBain AJ,Butler JA,Banks CE,Whitehead KA.Antimicrobial efficacy and synergy of metal ions against Enterococcus faecium,Klebsiella pneumonia and Acinetobacter baumanniiinplanktonicandbiofilm phenotypes[J].Sci Rep,2017,7(1):5911.doi:10.1038/s41598-017-05976-9.
[5]郑淑华,穆小萍,黄瑞玉,卢春敏,王浩平.铁螯合剂和硝酸镓对碳青霉烯类耐药鲍曼不动杆菌生长的影响[J].广东医学,2016,37(4):489-491.
[6] Lemire JA,Harrison JJ,Turner RJ.Antimicrobial activity of metals:mechanisms,molecular targets and applications[J].Nat Rev Microbiol,2013,11(6):371-384.
[7]周赟,易竹君,阙克婷,张震,刘作金.铁离子通过ROS-乙酰化P53促进巨噬细胞M1型极化[J].第三军医大学学报,2018,40(1):45-52.
[8]张鹏云,刘马峰,程安春.细菌铁离子利用系统与宿主抗感染免疫[J].生命科学研究,2016,20(1):82-88.
[9] Eijkelkamp BA, Hassan KA,Paulsen IT,Brown MH.Investigation ofthehumanpathogenAcinetobacter baumannii under iron limiting conditions[J]. BMC Genomics,2011,12:126.doi:10.1186/1471-2164-12-126.
[10] Antunes LC,Imperi F,Towner KJ,Visca P.Genomeassisted identification of putative iron-utilization genes in Acinetobacter baumannii and their distribution among a genotypically diverse collection of clinical isolates[J].Res Microbiol,2011,162(3):279-284.
[11] Koster W.Cytoplasmic membrane iron permease systems in the bacterial cell envelope[J].Front Biosci,2005,10:462-477.
[12] Wandersman C,Delepelaire P.Bacterial iron sources:from siderophores to hemophores[J].Annu Rev Microbiol,2004,58:611-647.
[13] MiethkeM, MarahielMA. Siderophore-basediron acquisition and pathogen control[J].Microbiol Mol Biol Rev,2007,71(3):413-451.
[14] Koronakis V,Eswaran J,Hughes C.Structure and function of TolC:the bacterial exit duct for proteins and drugs[J].Annu Rev Biochem,2004,73:467-489.
[15] Catel-Ferreira M,Marti S,Guillon L,Jara L,Coadou G,Molle V,Bouffartigues E,Bou G,Shalk I,Jouenne T,Vila-Farrés X,DéE.The outer membrane porin OmpW of Acinetobacter baumannii is involved in iron uptake and colistin binding[J].FEBS Lett,2016,590(2):224-231.
[16] Modarresi F,Azizi O,Shakibaie MR,Motamedifar M,Valibeigi B,Mansouri S.Effect of iron on expression of efflux pump(adeABC)and quorum sensing(luxI,luxR)genes in clinical isolates of Acinetobacter baumannii[J].APMIS,2015,123(11):959-968.
[17] Cucarella C,Solano C,Valle J,Amorena B,Lasa I,Penadés JR.Bap,a Staphylococcus aureus surface protein involved in biofilm formation[J].J Bacteriol,2001,183(9):2888-2896.
[18] Belenky P,Ye JD,Porter CB,Cohen NR,Lobritz MA,Ferrante T,Jain S,Korry BJ,Schwarz EG,Walker GC,Collins JJ.Bactericidal antibiotics induce toxic metabolic perturbations that lead to cellular damage[J].Cell Rep,2015,13(5):968-980.
[19] Yeom J,Imlay JA,Park W.Iron homeostasis affects antibiotic-mediated cell death in Pseudomonas species[J].J Biol Chem,2010,285(29):22689-22695.
[20] Yeom J,Jeon CO, Madsen EL,Park W.FerredoxinNADP+reductase from Pseudomonas putida functions as a ferric reductase[J].J Bacteriol,2009,191(5):1472-1479.
[21]谢芳.铁过载诱导ROS生成对造血干祖细胞功能的影响[D/OL].天津:天津医科大学,2012.http://cdmd.cnki.com.cn/Article/CDMD-10062-1012497576.htm.
[22] Rajendran M.Quinones as photosensitizer for photodynamic therapy:ROS generation, mechanism and detection methods[J]. Photodiag Photodyn Ther, 2016, 13:175-187.
[23] Prasad AS.Discovery of human zinc deficiency:its impact on human health and disease[J].Adv Nutr,2013,4(2):176-190.
[24] Andreini C,Banci L,Bertini I,Rosato A.Zinc through the three domains of life[J].J Proteome Res,2006,5(11):3173-3178.
[25] Nairn BL,Lonergan ZR,Wang J,Braymer JJ,Zhang Y,Calcutt MW,Lisher JP,Gilston BA,Chazin WJ,de CrécyLagard V, Giedroc DP,Skaar EP. The response of Acinetobacter baumannii to zinc starvation[J].Cell Host Microbe,2016,19(6):826-836.
[26]张留辉.锌离子对肺炎链球菌影响的蛋白质组学研究[D/OL].广州:暨南大学,2010.http://cdmd.cnki.com.cn/Article/CDMD-10559-2010123802.htm.
[27] Lin DL,Tran T,Alam JY,Herron SR,Ramirez MS,TolmaskyME. Inhibitionofaminoglycoside6′-Nacetyltransferase type Ib by zinc:reversal of amikacin resistance in Acinetobacter baumannii and Escherichia coli by a zinc ionophore[J].Antimicrob Agents Chemother,2014,58(7):4238-4241.
[28] Hood MI,Mortensen BL,Moore JL,Zhang Y,Kehl-Fie TE,Sugitani N,Chazin WJ,Caprioli RM,Skaar EP.IdentificationofanAcinetobacterbaumanniizinc acquisition system that facilitates resistance to calprotectinmediated zinc sequestration[J].PLoS Pathog,2012,8(12):e1003068.
[29]王晓岚.金属离子的抗菌性能及其抗菌机理研究[D/OL].广州:华南理工大学,2015.http://cdmd.cnki.com.cn/Article/CDMD-10561-1015988065.htm.
[30] Brandtzaeg P,Gabrielsen TO,Dale I,Müller F,Steinbakk M,Fagerhol MK.The leucocyte protein L1(calprotectin):aputative nonspecific defence factor at epithelial surfaces[J].Adv Exp Med Biol,1995,371A:201-206.
[31] van Faassen H,Kuolee R,Harris G,Zhao X,Conlan JW,Chen W. Neutrophils play an important role in host resistance to respiratory infection with Acinetobacter baumannii in mice[J].Infect Immun,2007,75(12):5597-5608.
[32] Ghasemi F,Jalal R.Antimicrobial action of zinc oxide nanoparticles in combination with ciprofloxacin and ceftazidimeagainstmultidrug-resistantAcinetobacter baumannii[J].J Glob Antimicrob Resist,2016,6:118-122.
[33] Huang HI,Shih HY,Lee CM,Yang TC,Lay JJ,Lin YE.In vitro efficacy of copper and silver ions in eradicating Pseudomonas aeruginosa,Stenotrophomonas maltophilia and Acinetobacterbaumannii:implicationsforon-site disinfection for hospital infection control[J].Water Res,2008,42(1-2):73-80.
[34]lamborováI,ZajícováV,Karpí2kováJ,Exnar P,Stibor I.New type of protective hybrid and nanocomposite hybrid coatings containing silver and copper with an excellent antibacterial effect especially against MRSA[J].Mater Sci Eng C Mater Biol Appl,2013,33(1):265-273.
[35] de Moraes AC,Lima BA,de Faria AF,Brocchi M,Alves OL.Graphene oxide-silver nanocomposite as a promising biocidal agent against methicillin-resistant Staphylococcus aureus[J].Int J Nanomed,2015,10:6847-6861.
[36] Weber BS,Kinsella RL,Harding CM,Feldman MF.The secrets of Acinetobacter secretion[J].Trends Microbiol,2017,25(7):532-545.
[37] García-Quintanilla M,Pulido MR,López-Rojas R,Pachón J, McConnell MJ. Emerging therapies for multidrug resistant Acinetobacter baumannii[J].Trends Microbiol,2013,21(3):157-163.