Evaluation of Amoebicidal Potential of Paneth Cell Cryptdin-2 against Entamoeba histolytica 英文参考文献.docVIP

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Evaluation of Amoebicidal Potential of Paneth Cell Cryptdin-2 against Entamoeba histolytica 英文参考文献.doc

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Evaluation of Amoebicidal Potential of Paneth Cell Cryptdin-2 against Entamoeba histolytica 英文参考文献

EvaluationofAmoebicidalPotentialofPanethCell Cryptdin-2againstEntamoebahistolytica SimranPreet1,SanjayBharati2,GeetaShukla1,AshwaniKoul2,PraveenRishi1* 1Department of Microbiology, Basic Medical Sciences Block, Panjab University, Chandigarh, India, 2Department of Biophysics, Basic Medical Sciences Block, Panjab University,Chandigarh,India Abstract Background:Amoebiasisisamajorpublichealthproblemintropicalandsubtropicalcountries.Currently,metronidazoleis thegoldchoicemedicationforthetreatmentofthisdisease.However,reportshaveindicatedtowardsthepossibility of developmentofmetronidazole-resistanceinEntamoebastrainsinnearfuture.Inviewoftheemergenceofthispossibility,in additiontotheassociatedsideeffectsandmutagenicabilityofthecurrentlyavailableanti-amoebicdrugs,thereisaneedto explorenewertherapeuticsagainstthisdisease.Inthiscontext,thepresentstudyevaluatedtheamoebicidalpotentialof cryptdin-2againstE.histolytica. Methods/Principal Findings: In the present study, cryptdin-2 exhibited potent in-vitro amoebicidal activity against E. histolytica in a concentration dependent manner at a minimum amoebicidal concentration (MAC) of 4mg/L. Scanning electronmicroscopyaswellasphasecontrastmicroscopicinvestigationsofcryptdin-2treatedtrophozoitesrevealedthat the peptide was able to induce significant morphological alterations in terms of membrane wrinkling, leakage of the cytoplasmiccontentsanddamagedplasmamembranesuggestingapossiblemembranedependentamoebicidalactivity. N-phenylnapthylamine(NPN)uptakeassayinpresenceofsulethal,lethalaswellastwicethelethalconcentrationsfurther confirmedthemembrane-dependentmodeofactionofcryptdin-2andsuggestedthatthepeptidecouldpermeabilizethe plasmamembraneofE.histolytica.Itwasalsofoundthatcryptdin-2interferedwithDNA,RNAaswellasproteinsynthesisof E.histolyticaexertingthehighesteffectagainstDNAsynthesis.Thus,themacromolecularsynthesisstudiescorrelatedwell withtheobservationsofmembranepermeabilizationstudies. Significance/Conclusions:Theamoebic