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Hydrophilic/hydrophobiccharactersofantimicrobialpeptidesderivedfromanimalsandtheireffectsonmultidrugresistantclinicalisolates

DOI: 10.13918/j.issn.2095-8137.2015.1.41, PP. 41-47

Keywords: Hydrophilic/hydrophobiccharacter,Multidrugresistantclinicalisolate,Cathelicidin-BF,TachyplesinIII

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Abstract:

Multidrugresistant(MDR)pathogeninfectionsareseriousthreatstohospitalizedpatientsbecauseofthelimitedtherapeuticoptions.Anovelgroupofantibioticcandidates,antimicrobialpeptides(AMPs),haverecentlyshownpowerfulactivitiesagainstbothGram-negativeandGram-positivebacteria.Unfortunately,theviabilityofusingtheseAMPsinclinicalsettingsremainstobeseen,sincemoststillneedtobeevaluatedpriortoclinicaltrialsandnotallofAMPsarepotentagainstMDRclinicalisolates.TofindaconnectionbetweenthecharacteristicsofseveraloftheseAMPsandtheireffectsagainstMDRpathogens,weselected14AMPsofanimaloriginwithtypicalstructuresandevaluatedtheirinvitroactivitiesagainstclinicalstrainsofextensivedrug-resistantAcinetobacterbaumannii,methicillin-resistantStaphylococcusaureus,extendedspectrumβ-lactamase-producingPseudomonasaeruginosaandextendedspectrumβ-lactamase-producingEscherichiacoli.Ourresultsshowedthatthesepeptides'hydrophilic/hydrophobiccharacteristics,ratherthantheirsecondarystructures,mayexplaintheirantibacterialeffectsontheseclinicalisolates.PeptidesthatareamphipathicalongthelongitudinaldirectionseemedtobeeffectiveagainstGram-negativepathogens,whilepeptideswithhydrophilicterminalsseparatedbyahydrophobicintermediatesectionappearedtobeeffectiveagainstbothGram-negativeandGram-positivepathogens.Amongthese,cathelicidin-BFwasfoundtoinhibitalloftheGram-negativepathogenstestedatdosagesofnomorethan16mg/L,killingapandrug-resistantA.baumanniistrainwithin2hat4×MICsand4hat2×MICs.TachyplesinIIIwasalsofoundcapableofinhibitingallGram-negativeandGram-positivepathogenstestedatnomorethan16mg/L,andsimilarlykilledthesameA.baumanniistrainwithin4hat4×MICsand2×MICs.Theseresultssuggestthatbothcathelicidin-BFandtachyplesinIIIarelikelyviabletargetsforthedevelopmentofAMPsforclinicaluses.

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