A Novel High Throughput Assay for Anthelmintic Drug Screening and Resistance Diagnosis by Real-Time Monitoring of Parasite Motility 英文参考文献.docVIP
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A Novel High Throughput Assay for Anthelmintic Drug Screening and Resistance Diagnosis by Real-Time Monitoring of Parasite Motility 英文参考文献
ANovelHighThroughputAssayforAnthelminticDrug
ScreeningandResistanceDiagnosisbyReal-Time
MonitoringofParasiteMotility
MichaelJ.Smout1,AndrewC.Kotze2,JamesS.McCarthy3,AlexLoukas1*
1JamesCookUniversity,Cairns,Australia,2CSIROLivestockIndustries,Brisbane,Australia,3QueenslandInstituteofMedicalResearch,Brisbane,Australia
Abstract
Background: Helminth parasites cause untold morbidity and mortality to billions of people and livestock. Anthelmintic
drugsareavailablebutresistanceisaprobleminlivestockparasites,andisaloomingthreatforhumanhelminths.Testing
the efficacy of available anthelmintic drugs and development of new drugs is hindered by the lack of objective high-
throughputscreeningmethods.Currently,drugeffectisassessedbyobservingmotilityordevelopmentofparasitesusing
laborious,subjective,low-throughputmethods.
Methodology/PrincipalFindings:Herewedescribeanovelapplicationforareal-timecellmonitoringdevice(xCELLigence)
thatcansimplyandobjectivelyassessanthelminticeffectsbymeasuringparasitemotilityinrealtimeinafullyautomated
high-throughputfashion.WequantitativelyassessedmotilityanddeterminedrealtimeIC50valuesofdifferentanthelmintic
drugs against several developmental stages of major helminth pathogens of humans and livestock, including larval
HaemonchuscontortusandStrongyloidesratti,andadulthookwormsandbloodflukes.Theassayenabledquantificationof
theonsetofegghatchinginrealtime,andtheimpactofdrugsonhatchrate,aswellasdiscriminatingbetweentheeffects
ofdrugsonmotilityofdrug-susceptibleand–resistantisolatesofH.contortus.
Conclusions/Significance:Ourfindingsindicatethatthistechniquewillbesuitablefordiscoveryanddevelopmentofnew
anthelmintic drugs as well as for detection of phenotypic resistance to existing drugs for the majority of helminths and
otherpathogenswheremotilityisameasureofpathogenviability.Themethodisalsoamenabletouseforotherpurposes
wheremotilityisassessed,suchasgenesilencingorantibody-mediatedkilling.
Citation:SmoutMJ,KotzeAC,McCarthyJS,LoukasA(2010)ANovelHighThr
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