Bacillus thuringiensis Cry5B Protein Is Highly Efficacious as a Single-Dose Therapy against an Intestinal Roundworm Infection in Mice 英文参考文献.docVIP

BacillusthuringiensisCry5BProteinIsHighlyEfficacious asaSingle-DoseTherapyagainstanIntestinal RoundwormInfectioninMice YanHu.,SophiaB.Georghiou.,AlanJ.Kelleher,RaffiV.Aroian* SectionofCellandDevelopmentalBiology,UniversityofCalifornia,SanDiego,LaJolla,California,UnitedStatesofAmerica Abstract Background: Intestinal parasitic nematode diseases are one of the great diseases of our time. Intestinal roundworm parasites,includinghookworms,whipworms,andAscaris,infectwellover1billionpeopleandcausesignificantmorbidity, especiallyinchildrenandpregnantwomen.Todate,thereisonlyonedrug,albendazole,withadequateefficacyagainst these parasites to be used in mass drug administration, although tribendimidine may emerge as a second. Given the hundredsofmillionsofpeopletobetreated,thethreatofparasiteresistance,andtheinadequacyofcurrenttreatments, new anthelmintics are urgently needed. Bacillus thuringiensis (Bt) crystal (Cry) proteins are the most common used biologicallyproducedinsecticidesintheworldandareconsiderednon-toxictovertebrates. Methods/Principal Findings: Here westudy the ability of anematicidal Cry protein, Cry5B, toeffect a curein mice of a chronic roundworm infection caused by the natural intestinal parasite, Heligmosomoides bakeri (formerly polygyrus ). We showthatCry5BproducedfromeitheroftwoBtstrainscanactasananthelminticinvivowhenadministeredasasingle dose,achievinga,98%reductioninparasiteeggproductionand,70%reductioninwormburdenswhendeliveredperos at,700nmoles/kg(90–100mg/kg).Furthermore,ourdata,combinedwiththefindingsofothers,suggestthattherelative efficacyofCry5Biseithercomparableorsuperiortocurrentanthelmintics.WealsodemonstratethatCry5Bislikelytobe degradedquiterapidlyinthestomach,suggestingthattheactualdosereachingtheparasitesisverysmall. Conclusions/Significance:ThisstudyindicatesthatBtCryproteinssuchasCry5Bhaveexcellentanthelminticpropertiesin vivoandthatproperformulationoftheproteinislikelytorevealasuperioranthelmintic. Citation:HuY,GeorghiouSB,KelleherAJ,A