Differential Expression of Type III Effector BteA Protein Due to IS481 Insertion in Bordetella pertussis 英文参考文献.docVIP

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Differential Expression of Type III Effector BteA Protein Due to IS481 Insertion in Bordetella pertussis 英文参考文献.doc

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Differential Expression of Type III Effector BteA Protein Due to IS481 Insertion in Bordetella pertussis 英文参考文献

DifferentialExpressionofTypeIIIEffectorBteAProtein DuetoIS481InsertioninBordetellapertussis Hyun-JaHan1¤,AsaomiKuwae2,AkioAbe2,YoshichikaArakawa1,KazunariKamachi1* 1Department ofBacteriologyII, NationalInstitute ofInfectious Diseases, Tokyo,Japan, 2Laboratory ofBacterialInfection,Kitasato Institute for LifeSciences,Kitasato University,Tokyo,Japan Abstract Background:Bordetellapertussisistheprimaryetiologicagentofthediseasepertussis.Universalimmunizationprograms have contributed to a significant reduction in morbidity and mortality of pertussis; however, incidence of the disease, especiallyinadolescentsandadults,hasincreasedinseveralcountriesdespitehighvaccinationcoverage.Duringthelast three decades, strains of Bordetella pertussis in circulation have shifted from the vaccine-type to the nonvaccine-type in manycountries.Acomparativeproteomicanalysisofthestrainswasperformedtoidentifyprotein(s)involvedinthetype shift. Methodology/PrincipalFinding:ProteomicanalysisidentifiedonedifferentiallyexpressedproteinintheB.pertussisstrains: thetypeIIIcytotoxiceffectorproteinBteA,whichisresponsibleforhostcelldeathinBordetellabronchisepticainfections. Immunoblot analysis confirmed the prominent expression of BteA protein in the nonvaccine-type strains but not in the vaccine-typestrains.Sequenceanalysisofthevaccine-typestrainsrevealedanIS481insertioninthe59untranslatedregion ofbteA,2136bpupstreamofthebteAstartcodon.AhighlevelofbteAtranscriptsfromtheIS481promoterwasdetected inthevaccine-typestrains,indicatingthatthetranscriptmightbeanuntranslatableform.Furthermore,BteAmutantstudies demonstratedthatBteAexpressioninthevaccine-typestrainsisdown-regulatedbytheIS481insertion. Conclusion/Significance:ThecytotoxiceffectorBteAproteinisexpressedathigherlevelsinB.pertussisnonvaccine-type strainsthaninvaccine-typestrains.Thistype-dependentexpressionisduetoaninsertionofIS481inB.pertussisclinical strains,suggestingthataugmentedexpressionofBteAproteinmightplayakeyroleinthetypeshiftofB.pertussi