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Impact of different cell penetrating peptides on the efficacy of antisense therapeutics for targeting intracellular pathogens

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dc.contributor.authorAbushahba, Mostafa FN N.en
dc.contributor.authorMohammad, Haroonen
dc.contributor.authorThangamani, Shankaren
dc.contributor.authorHussein, Asmaa AA A.en
dc.contributor.authorSeleem, Mohamed N.en
dc.date.accessioned2020-09-21T16:15:04Zen
dc.date.available2020-09-21T16:15:04Zen
dc.date.issued2016-02-10en
dc.date.updated2020-09-21T16:15:03Zen
dc.description.abstractThere is a pressing need for novel and innovative therapeutic strategies to address infections caused by intracellular pathogens. Peptide nucleic acids (PNAs) present a novel method to target intracellular pathogens due to their unique mechanism of action and their ability to be conjugated to cell penetrating peptides (CPP) to overcome challenging delivery barriers. In this study, we targeted the RNA polymerase α subunit (rpoA) using a PNA that was covalently conjugated to five different CPPs. Changing the conjugated CPP resulted in a pronounced improvement in the antibacterial activity observed against Listeria monocytogenes in vitro, in cell culture, and in a Caenorhabditis elegans (C. elegans) infection model. Additionally, a time-kill assay revealed three conjugated CPPs rapidly kill Listeria within 20 minutes without disrupting the bacterial cell membrane. Moreover, rpoA gene silencing resulted in suppression of its message as well as reduced expression of other critical virulence genes (Listeriolysin O, and two phospholipases plcA and plcB) in a concentration-dependent manner. Furthermore, PNA-inhibition of bacterial protein synthesis was selective and did not adversely affect mitochondrial protein synthesis. This study provides a foundation for improving and developing PNAs conjugated to CPPs to better target intracellular pathogens.en
dc.description.versionPublished versionen
dc.format.extent12 page(s)en
dc.format.mediumElectronicen
dc.format.mimetypeapplication/pdfen
dc.identifierARTN 20832 (Article number)en
dc.identifier.doihttps://doi.org/10.1038/srep20832en
dc.identifier.eissn2045-2322en
dc.identifier.issn2045-2322en
dc.identifier.issue1en
dc.identifier.orcidSeleem, Mohamed [0000-0003-0939-0458]en
dc.identifier.othersrep20832 (PII)en
dc.identifier.pmid26860980 (pubmed)en
dc.identifier.urihttp://hdl.handle.net/10919/100035en
dc.identifier.volume6en
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectRESISTANT STAPHYLOCOCCUS-AUREUSen
dc.subjectCAENORHABDITIS-ELEGANS INFECTIONen
dc.subjectENTERICA SEROVAR TYPHIMURIUMen
dc.subjectLISTERIA-MONOCYTOGENESen
dc.subjectGENE-EXPRESSIONen
dc.subjectESCHERICHIA-COLIen
dc.subjectPURE CULTUREen
dc.subjectMODEL HOSTen
dc.subjectINHIBITIONen
dc.subjectBACTERIALen
dc.subject.meshAnimalsen
dc.subject.meshCaenorhabditis elegansen
dc.subject.meshListeria monocytogenesen
dc.subject.meshDNA-Directed RNA Polymerasesen
dc.subject.meshBacterial Proteinsen
dc.subject.meshOligonucleotides, Antisenseen
dc.subject.meshPeptide Nucleic Acidsen
dc.subject.meshAnti-Bacterial Agentsen
dc.subject.meshMicrobial Sensitivity Testsen
dc.subject.meshVirulenceen
dc.subject.meshAmino Acid Sequenceen
dc.subject.meshCell-Penetrating Peptidesen
dc.titleImpact of different cell penetrating peptides on the efficacy of antisense therapeutics for targeting intracellular pathogensen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2016-01-08en
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/CVM T&R Facultyen
pubs.organisational-group/Virginia Techen

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