Molecular Mechanisms of Drug Resistance in Natural Leishmania Populations Vary with Genetic Background 英文参考文献.docVIP
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Molecular Mechanisms of Drug Resistance in Natural Leishmania Populations Vary with Genetic Background 英文参考文献
MolecularMechanismsofDrugResistanceinNatural
LeishmaniaPopulationsVarywithGeneticBackground
SaskiaDecuypere1,2,3,ManuVanaerschot1,KirstynBrunker2,HideoImamura1,4,SylkeMu¨ller3 ,Basudha
Khanal5,SumanRijal5,Jean-ClaudeDujardin1,6*,GrahamH.Coombs2
1Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium, 2Strathclyde Institute of Pharmacy and Biomedical Sciences, University of
Strathclyde,Glasgow,Scotland,UnitedKingdom,3WellcomeTrustCentreforMolecularParasitology,InstituteofInfection,ImmunityandInflammation,CollegeofMedical,
VeterinaryandLifeSciences,UniversityofGlasgow,Glasgow,Scotland,UnitedKingdom,4WellcomeTrustSangerInstitute,WellcomeTrustGenomeCampus,Hinxton,
England,UnitedKingdom,5B.P.KoiralaInstituteofHealthSciences,Ghopa,Dharan,Nepal,6DepartmentofBiomedicalSciences,UniversityofAntwerp,Antwerp,Belgium
Abstract
Theevolutionofdrug-resistanceinpathogensisamajorglobalhealththreat.Elucidatingthemolecularbasisofpathogen
drug-resistancehasbeenthefocusofmanystudiesbutrarelyisitknownwhetheradrug-resistancemechanismidentifiedis
universal for the studied pathogen; it has seldom been clarified whether drug-resistance mechanisms vary with the
pathogen’sgenotype.Neverthelessthisisofcriticalimportanceingaininganunderstandingofthecomplexityofthisglobal
threatandinunderpinningepidemiologicalsurveillanceofpathogendrugresistanceinthefield.Thisstudyaimedtoassess
themolecularandphenotypicheterogeneitythatemergesinnaturalparasitepopulationsunderdrugtreatmentpressure.
WestudiedlinesoftheprotozoanparasiteLeishmania(L.)donovaniwithdifferentialsusceptibilitytoantimonialdrugs;the
linesbeingderivedfromclinicalisolatesbelongingtotwodistinctgeneticpopulationsthatcirculateintheleishmaniasis
endemic region of Nepal. Parasite pathways known to be affected by antimonial drugs were characterised on five
experimental levels in the lines of the two populations. Characterisation of DNA sequence, gene expression, protein
expressionandthiollevelsrevealedanumberofmolecular
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