结核分枝杆菌抗原PE 35和PPE 68基因多态性的初步研究

仇艳 蒋毅 刘海灿 李马超 万康林

仇艳, 蒋毅, 刘海灿, 李马超, 万康林. 结核分枝杆菌抗原PE 35和PPE 68基因多态性的初步研究[J]. 疾病监测, 2015, 30(7): 539-545. doi: 10.3784/j.issn.1003-9961.2015.07.005
引用本文: 仇艳, 蒋毅, 刘海灿, 李马超, 万康林. 结核分枝杆菌抗原PE 35和PPE 68基因多态性的初步研究[J]. 疾病监测, 2015, 30(7): 539-545. doi: 10.3784/j.issn.1003-9961.2015.07.005
QIU Yan, JIANG Yi, LIU Hai-can, LI Ma-chao, WAN Kang-lin. Polymorphism of antigens PE 35 and PPE 68 genes of Mycobacterium tuberculosis[J]. Disease Surveillance, 2015, 30(7): 539-545. doi: 10.3784/j.issn.1003-9961.2015.07.005
Citation: QIU Yan, JIANG Yi, LIU Hai-can, LI Ma-chao, WAN Kang-lin. Polymorphism of antigens PE 35 and PPE 68 genes of Mycobacterium tuberculosis[J]. Disease Surveillance, 2015, 30(7): 539-545. doi: 10.3784/j.issn.1003-9961.2015.07.005

结核分枝杆菌抗原PE 35和PPE 68基因多态性的初步研究

doi: 10.3784/j.issn.1003-9961.2015.07.005
基金项目: 

国家自然科学基金(No.81401647)

国家科技重大专项(No.2013ZX10003006, 2013ZX10003002-001)

Polymorphism of antigens PE 35 and PPE 68 genes of Mycobacterium tuberculosis

Funds: 

This study were supported by the fund for the Project from National Natural Science Foundation (No.81401647) and the fund for the National Science and Technology Key Project for Priority Communicable Disease Prevention and Control (No.2013ZX10003006,2013ZX10003002-001)

  • 摘要: 目的 为研究结核分枝杆菌RD1区编码PE/PPE蛋白家族中的PE 35和PPE 68基因的多态性,并评估其基因多态性对免疫识别的影响。方法 笔者从本实验室保存的来自国内不同地区的2346株结核分枝杆菌复合群临床分离株中,选取代表不同Spoligotyping类型的161 株临床分离结核分枝杆菌菌株,基因扩增后进行序列比对,比较其在T细胞抗原表位的差异。结果 在161 株菌株中,23 株显示有PE 35基因多态性,8 株有PPE 68基因多态性。在PE 35基因中,除了菌株JL06018的突变外的其余突变都导致其T细胞抗原表位的改变。PPE 68基因中,62个T细胞表位中有58个(占93.5%)发生了改变。非北京家族PE 35基因的突变率明显高于北京家族 (P0.05),而PPE 68基因突变虽是非北京家族高于北京家族,但差异无统计学意义。结论 PE 35和PPE 68的编码基因存在明显的多态性,并很有可能导致蛋白功能的明显改变。此外,这2个蛋白的人类T细胞表位是高度可变的,提示这2种蛋白可能通过参与分化选择来逃避宿主免疫。北京家族可能比非北京家族更容易被宿主T细胞识别,进而更容易传播。
  • [1] MahairasGG,SaboPJ,HickeyMJ,etal.MolecularanalysisofgeneticdifferencesbetweenMycobacteriumbovisBCGandvirulentM.bovis[J].JBacteriol,1996,178(5):1274-1282.
    [2] LiuXQ,DosanjhD,VariaH,etal.EvaluationofT-cellresponsestonovelRD1-andRD2-encodedMycobacteriumtuberculosisgeneproductsforspecificdetectionofhumantuberculosisinfection[J].InfectImmun,2004,72(5):2574-2581.
    [3] HanifSN,El-ShammyAM,Al-AttiyahR,etal.WholebloodassaystoidentifyTh1cellantigensandpeptidesencodedbyMycobacteriumtuberculosis-specificRD1genes[J].MedPrincPract,2008,17(3):244-249.
    [4] MustafaAS,Al-AttiyahR,HanifSN,etal.EfficienttestingoflargepoolsofMycobacteriumtuberculosisRD1peptidesandidentificationofmajorantigensandimmunodominantpeptidesrecognizedbyhumanTh1cells[J].ClinVaccineImmunol,2008,15(6):916-924.
    [5] HanifSN,Al-AttiyahR,MustafaAS.Species-specificantigenicMycobacteriumtuberculosisproteinstestedbydelayed-typehypersensitivityresponse[J].IntJTubercLungDis,2010,14(4):489-494.
    [6] PymAS,BrodinP,BroschR,etal.LossofRD1contributedtotheattenuationofthelivetuberculosisvaccinesMycobacteriumbovisBCGandMycobacteriummicroti[J].MolMicrobiol,2002,46(3):709-717.
    [7] LewisKN,LiaoR,GuinnKM,etal.DeletionofRD1fromMycobacteriumtuberculosismimicsbacilleCalmette-Guerinattenuation[J].JInfectDis,2003,187(1):117-123.
    [8] MalaghiniM,Thomaz-SoccolV,ProbstCM,etal.Recombinantantigenproductionforassaysofintradermoreactionfordiagnosisandsurveillanceoftuberculosis[J].JBiotechnol,2011,156(1):56-58.
    [9] MukhopadhyayS,BalajiKN.ThePEandPPEproteinsofMycobacteriumtuberculosis[J].Tuberculosis,2011,91(5):441-447.
    [10] SampsonSL.MycobacterialPE/PPEproteinsatthehost-pathogeninterface[J].ClinDevImmunol,2011,2011:497203.
    [11] AkhterY,EhebauerMT,MukhopadhyayS,etal.ThePE/PPEmultigenefamilycodesforvirulencefactorsandisapossiblesourceofmycobacterialantigenicvariation:perhapsmore?[J].Biochimie,2012,94(1):110-116.
    [12] McEvoyCRE,CloeteR,MullerB,etal.ComparativeanalysisofMycobacteriumtuberculosispeandppegenesrevealshighsequencevariationandanapparentabsenceofselectiveconstraints[J].PLoSOne,2012,7(4):e30593.
    [13] CopinR,CoscollM,SeiffertSN,etal.Sequencediversityinthepe_pgrsgenesofMycobacteriumtuberculosisisindependentofhumanTcellrecognition[J].mBio,2014,5(1):e00960-13.
    [14] LarkinMA,BlackshieldsG,BrownNP,etal.ClustalWandClustalXversion2.0[J].Bioinformatics,2007,23(21):2947-2948.
    [15] KimY,PonomarenkoJ,ZhuZ,etal.Immuneepitopedatabaseanalysisresource[J].NucleicAcidsRes,2012,40(WebServerissue):W525-W530.
    [16] OkkelsLM,BrockI,FollmannF,etal.PPEprotein(Rv3873)fromDNAsegmentRD1ofMycobacteriumtuberculosis:strongrecognitionofbothspecificT-cellepitopesandepitopesconservedwithinthePPEfamily[J].InfectImmun,2003,71(11):6116-6123.
    [17] OkkelsLM,AndersenP.Protein-proteininteractionsofproteinsfromtheESAT-6familyofMycobacteriumtuberculosis[J].JBacteriol,2004,186(8):2487-2491.
    [18] TeutschbeinJ,SchumannG,MollmannU,etal.AproteinlinkagemapoftheESAT-6secretionsystem1(ESX-1)ofMycobacteriumtuberculosis[J].MicrobiolRes,2009,164(3):253-259.
    [19] TiwariB,SooryA,RaghunandTR.AnimmunomodulatoryrolefortheMycobacteriumtuberculosisregionofdifference1locusproteinsPE35(Rv3872)andPPE68(Rv3873)[J].FebsJ,2014,281(6):1556-1570.
    [20] BrodinP,MajlessiL,MarsollierL,etal.DissectionofESAT-6system1ofMycobacteriumtuberculosisandimpactonimmunogenicityandvirulence[J].InfectImmun,2006,74(1):88-98.
    [21] VordermeierHM,HewinsonRG,WilkinsonRJ,etal.ConservedimmunerecognitionhierarchyofmycobacterialPE/PPEproteinsduringinfectioninnaturalhosts[J].PLoSOne,2012,7(8):e40890.
    [22] ComasI,ChakravarttiJ,SmallPM,etal.HumanTcellepitopesofMycobacteriumtuberculosisareevolutionarilyhyperconserved[J].NatGenet,2010,42(6):498-503.
    [23] ParwatiDI,vanCrevelR,vanSoolingenD.PossibleunderlyingmechanismsforsuccessfulemergenceoftheMycobacteriumtuberculosisBeijinggenotypestrains[J].LancetInfectDis,2010,10(2):103-111.
    [24] KwanCK,ErnstJD.HIVandtuberculosis:adeadlyhumansyndemic[J].ClinMicrobiolRev,2011,24(2):351-376.
    [25] MukherjeeP,DuttaM,DattaP,etal.TheRD1-encodedantigenRv3872ofMycobacteriumtuberculosisasapotentialcandidateforserodiagnosisoftuberculosis[J].ClinMicrobiolInfect,2007,13(2):146-152.
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出版历程
  • 收稿日期:  2015-02-11
  • 刊出日期:  2015-07-20

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