恶性疟原虫药物抗性相关基因筛选与鉴定方法
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摘要
恶性疟原虫(Plasmodium falciparum)几乎对所有的抗疟药物都产生了抗性,近年来青蒿素类药物抗性的出现与扩散使全球疟疾控制与消除面临巨大挑战。筛选鉴定恶性疟原虫药物抗性相关基因对阐明抗疟药物作用机制、监测抗性的出现和扩散以及制定抗疟药物的使用规范都具有重要意义。本文对恶性疟原虫药物抗性基因常用的筛选与鉴定方法进行综述。
Plasmodium falciparum has developed resistance to almost all currently available antimalaria drugs.The emergence of resistance to artemisinin and the alike in recent years has greatly challenged the global malaria control and elimination. Thus, screening and identifying genes associated with the drug resistance is of great significance to elucidate the action mechanism of antimalarials, monitor the occurrence and spread of resistance, and set up guidelines for antimalarial drug use. This paper summarizes the approaches to screen and identify the genes associated with drug resistance of P. falciparum.
Plasmodium falciparum has developed resistance to almost all currently available antimalaria drugs.The emergence of resistance to artemisinin and the alike in recent years has greatly challenged the global malaria control and elimination. Thus, screening and identifying genes associated with the drug resistance is of great significance to elucidate the action mechanism of antimalarials, monitor the occurrence and spread of resistance, and set up guidelines for antimalarial drug use. This paper summarizes the approaches to screen and identify the genes associated with drug resistance of P. falciparum.
引文
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[15]Foote SJ,Kyle DE,Martin RK,et al.Several alleles of the multidrug-resistance gene are closely linked to chloroquine resistance in Plasmodium falciparum[J].Nature,1990,345(6272):255-258.
[16]Ranford-Cartwright LC,Mwangi JM.Analysis of malaria parasite phenotypes using experimental genetic crosses of Plasmodium falciparum[J].Int J Parasitol,2012,42(6):529-534.
[17]Su X,Kirkman LA,Fujioka H,et al.Complex polymorphisms in an approximately 330 k Da protein are linked to chloroquineresistant P.falciparum in Southeast Asia and Africa[J].Cell,1997,91(5):593-603.
[18]Wellems TE,Walker-Jonah A,Panton LJ.Genetic mapping of the chloroquine-resistance locus on Plasmodium falciparum chromos ome 7[J].Proc Natl Acad Sci USA,1991,88(8):3382-3386.
[19]Fidock D,Nomura T,Talley AK,et al.Mutations in the P.falciparum digestive vacuole transmembrane protein Pf CRT and evidence for their role in chloroquine resistance[J].Mol Cell,2000,6(4):861-871.
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[21]Sen S,Ferdig M.QTL analysis for discovery of genes involved in drug responses[J].Curr Drug Targets Infect Disord,2004,4(1):53-63.
[22]Cooper RA,Ferdig MT,Su XZ,et al.Alternative mutations at position 76 of the vacuolar transmembrane protein Pf CRT are associated with chloroquine resistance and unique stereospecific quinine and quinidine responses in Plasmodium falciparum[J].Mol Pharmacol,2002,61(1):35-42.
[23]Ferdig MT,Cooper RA,Mu J,et al.Dissecting the loci of low-level quinine resistance in malaria parasites[J].Mol Microbiol,2004,52(4):985-997.
[24]Van Tyne D,Park DJ,Schaffner SF,et al.Identification and functional validation of the novel antimalarial resistance locus PF10_0355 in Plasmodium falciparum[J].PLo S Genet,2011,7(4):e1001383.
[25]Cheeseman IH,Miller BA,Nair S,et al.A major genome region underlying artemisinin resistance in malaria[J].Science,2012,336(6077):79-82.
[26]Takala-Harrison S,Clark TG,Jacob CG,et al.Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia[J].Proc Natl Acad Sci USA,2013,110(1):240-245.
[27]Ariey F,Witkowski B,Amaratunga C,et al.A molecular marker of artemisinin-resistant Plasmodium falciparum malaria[J].Nature,2014,505(7481):50-55.
[28]Ghorbal M,Gorman M,Macpherson CR,et al.Genome editing in the human malaria parasite Plasmodium falciparum using the CRISPR-Cas9 system[J].Nat Biotechnol,2014,32(8):819-821.
[29]Straimer J,Gndig NF,Witkowski B,et al.Drug resistance.K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates[J].Science,2015,347(6220):428-431.
[30]Miotto O,Amato R,Ashley EA,et al.Genetic architecture of artemisinin-resistant Plasmodium falciparum[J].Nat Genet,2015,47(3):226-234.
[31]Witkowski B,Amaratunga C,Khim N,et al.Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia:in-vitro and ex-vivo drugresponse studies[J].Lancet Infect Dis,2013,13(12):1043-1049.
[32]Borrmann S,Straimer J,Mwai L,et al.Genome-wide screen identifies new candidate genes associated with artemisinin susceptibility in Plasmodium falciparum in Kenya[J].Sci Rep,2013,3:3318.
[33]Mu JB,Myers AR,Jiang H,et al.Plasmodium falciparum genome-wide scans for positive selection,recombination hot spots and resistance to antimalarial drugs[J].Nat Genet,2010,42(3):268-271.
[2]陈佩惠.疟原虫的生活史[J].生物学通报,1992,27(8):9-11.
[3]Noedl H,Se Y,Schaecher K,et al.Evidence of artemisininresistant malaria in western Cambodia[J].N Engl J Med,2008,359(24):2619-2620.
[4]Dondorp AM,Nosten F,Yi P,et al.Artemisinin resistance in Plasmodium falciparum malaria[J].N Engl J Med,2009,361(5):455-467.
[5]张逸龙,潘卫庆.恶性疟原虫对青蒿素产生抗性的研究进展[J].中国寄生虫学与寄生虫病杂志,2015,33(6):418-424.
[6]Ye R,Hu D,Zhang Y,et al.Distinctive origin of artemisininresistant Plasmodium falciparum on the China-Myanmar border[J].Sci Rep,2016,6:20100.
[7]赵绍敏,王满元.恶性疟原虫对青蒿素类药物产生耐药性的全球现状和基础研究[J].中国寄生虫学与寄生虫病杂志,2014,32(5):380-384.
[8]Diggens SM,Gutteridge WE,Trigg PI.Altered dihydrofolate reductase associated with a pyrimethamine-resistant Plasmodium berghei berghei produced in a single step[J].Nature,1970,228(5271):579-580.
[9]Cowman AF,Morry MJ,Biggs BA,et al.Amino acid changes linked to pyrimethamine resistance in the dihydrofolate reductasethymidylate synthase gene of Plasmodium falciparum[J].Proc Natl Acad Sci USA,1988,85(23):9109-9113.
[10]Peterson DS,Di Santi SM,Povoa M,et al.Prevalence of the dihydrofolate reductase Asn-108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the Brazilian Amazon[J].Am J Trop Med Hyg,1991,45(4):492-497.
[11]Peterson DS,Walliker D,Wellems TE.Evidence that a point mutation in dihydrofolate reductase-thymidylate synthase confers resistance to pyrimethamine in falciparum malaria[J].Proc Natl Acad Sci USA,1988,85(23):9114-9118.
[12]Wu Y,Kirkman LA,Wellems TE.Transformation of Plasmodium falciparum malaria parasites by homologous integration of plasmids that confer resistance to pyrimethamine[J].Proc Natl Acad Sci USA,1996,93(3):1130-1134.
[13]Srivastava IK,Morrisey JM,Darrouzet E,et al.Resistance mutations reveal the atovaquone binding domain of cytochrome b in malaria parasites[J].Mol Microbiol,1999,33(4):704-711.
[14]Korsinczky M,Chen N,Kotecka B,et al.Mutations in Plasmodium falciparum cytochrome b that are associated with atovaquone resistance are located at a putative drug-binding site[J].Antimicrob Agents Chemother,2000,44(8):2100-2108.
[15]Foote SJ,Kyle DE,Martin RK,et al.Several alleles of the multidrug-resistance gene are closely linked to chloroquine resistance in Plasmodium falciparum[J].Nature,1990,345(6272):255-258.
[16]Ranford-Cartwright LC,Mwangi JM.Analysis of malaria parasite phenotypes using experimental genetic crosses of Plasmodium falciparum[J].Int J Parasitol,2012,42(6):529-534.
[17]Su X,Kirkman LA,Fujioka H,et al.Complex polymorphisms in an approximately 330 k Da protein are linked to chloroquineresistant P.falciparum in Southeast Asia and Africa[J].Cell,1997,91(5):593-603.
[18]Wellems TE,Walker-Jonah A,Panton LJ.Genetic mapping of the chloroquine-resistance locus on Plasmodium falciparum chromos ome 7[J].Proc Natl Acad Sci USA,1991,88(8):3382-3386.
[19]Fidock D,Nomura T,Talley AK,et al.Mutations in the P.falciparum digestive vacuole transmembrane protein Pf CRT and evidence for their role in chloroquine resistance[J].Mol Cell,2000,6(4):861-871.
[20]S idhu ABS,Verdier-Pinard D,Fidock DA.Chloroquine resistance in Plasmodium falciparum malaria parasites conferred by pfcrt mutations[J].Science,2002,298(5591):210-213.
[21]Sen S,Ferdig M.QTL analysis for discovery of genes involved in drug responses[J].Curr Drug Targets Infect Disord,2004,4(1):53-63.
[22]Cooper RA,Ferdig MT,Su XZ,et al.Alternative mutations at position 76 of the vacuolar transmembrane protein Pf CRT are associated with chloroquine resistance and unique stereospecific quinine and quinidine responses in Plasmodium falciparum[J].Mol Pharmacol,2002,61(1):35-42.
[23]Ferdig MT,Cooper RA,Mu J,et al.Dissecting the loci of low-level quinine resistance in malaria parasites[J].Mol Microbiol,2004,52(4):985-997.
[24]Van Tyne D,Park DJ,Schaffner SF,et al.Identification and functional validation of the novel antimalarial resistance locus PF10_0355 in Plasmodium falciparum[J].PLo S Genet,2011,7(4):e1001383.
[25]Cheeseman IH,Miller BA,Nair S,et al.A major genome region underlying artemisinin resistance in malaria[J].Science,2012,336(6077):79-82.
[26]Takala-Harrison S,Clark TG,Jacob CG,et al.Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia[J].Proc Natl Acad Sci USA,2013,110(1):240-245.
[27]Ariey F,Witkowski B,Amaratunga C,et al.A molecular marker of artemisinin-resistant Plasmodium falciparum malaria[J].Nature,2014,505(7481):50-55.
[28]Ghorbal M,Gorman M,Macpherson CR,et al.Genome editing in the human malaria parasite Plasmodium falciparum using the CRISPR-Cas9 system[J].Nat Biotechnol,2014,32(8):819-821.
[29]Straimer J,Gndig NF,Witkowski B,et al.Drug resistance.K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates[J].Science,2015,347(6220):428-431.
[30]Miotto O,Amato R,Ashley EA,et al.Genetic architecture of artemisinin-resistant Plasmodium falciparum[J].Nat Genet,2015,47(3):226-234.
[31]Witkowski B,Amaratunga C,Khim N,et al.Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia:in-vitro and ex-vivo drugresponse studies[J].Lancet Infect Dis,2013,13(12):1043-1049.
[32]Borrmann S,Straimer J,Mwai L,et al.Genome-wide screen identifies new candidate genes associated with artemisinin susceptibility in Plasmodium falciparum in Kenya[J].Sci Rep,2013,3:3318.
[33]Mu JB,Myers AR,Jiang H,et al.Plasmodium falciparum genome-wide scans for positive selection,recombination hot spots and resistance to antimalarial drugs[J].Nat Genet,2010,42(3):268-271.