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dc.contributor.authorRajamuthiah, Rajmohanen_US
dc.contributor.authorJayamani, Elamparithien_US
dc.contributor.authorConery, Annie L.en_US
dc.contributor.authorFuchs, Beth Burgwynen_US
dc.contributor.authorKim, Wooseongen_US
dc.contributor.authorJohnston, Tatianaen_US
dc.contributor.authorVilcinskas, Andreasen_US
dc.contributor.authorAusubel, Frederick M.en_US
dc.contributor.authorMylonakis, Eleftheriosen_US
dc.date.accessioned2015-07-13T18:47:23Z
dc.date.issued2015en_US
dc.identifier.citationRajamuthiah, Rajmohan, Elamparithi Jayamani, Annie L. Conery, Beth Burgwyn Fuchs, Wooseong Kim, Tatiana Johnston, Andreas Vilcinskas, Frederick M. Ausubel, and Eleftherios Mylonakis. 2015. “A Defensin from the Model Beetle Tribolium castaneum Acts Synergistically with Telavancin and Daptomycin against Multidrug Resistant Staphylococcus aureus.” PLoS ONE 10 (6): e0128576. doi:10.1371/journal.pone.0128576. http://dx.doi.org/10.1371/journal.pone.0128576.en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:17295705
dc.description.abstractThe red flour beetle Tribolium castaneum is a common insect pest and has been established as a model beetle to study insect development and immunity. This study demonstrates that defensin 1 from T. castaneum displays in vitro and in vivo antimicrobial activity against drug resistant Staphylococcus aureus strains. The minimum inhibitory concentration (MIC) of defensin 1 against 11 reference and clinical staphylococcal isolates was between 16–64 μg/ml. The putative mode of action of the defensin peptide is disruption of the bacterial cell membrane. The antibacterial activity of defensin 1 was attenuated by salt concentrations of 1.56 mM and 25 mM for NaCl and CaCl2 respectively. Treatment of defensin 1 with the reducing agent dithiothreitol (DTT) at concentrations 1.56 to 3.13 mM abolished the antimicrobial activity of the peptide. In the presence of subinhibitory concentrations of antibiotics that also target the bacterial cell envelope such as telavancin and daptomycin, the MIC of the peptide was as low as 1 μg/ml. Moreover, when tested against an S. aureus strain that was defective in D-alanylation of the cell wall, the MIC of the peptide was 0.5 μg/ml. Defensin 1 exhibited no toxicity against human erythrocytes even at 400 μg/ml. The in vivo activity of the peptide was validated in a Caenorhabditis elegans-MRSA liquid infection assay. These results suggest that defensin 1 behaves similarly to other cationic AMPs in its mode of action against S. aureus and that the activity of the peptide can be enhanced in combination with other antibiotics with similar modes of action or with compounds that have the ability to decrease D-alanylation of the bacterial cell wall.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0128576en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4465704/pdf/en
dash.licenseLAAen_US
dc.titleA Defensin from the Model Beetle Tribolium castaneum Acts Synergistically with Telavancin and Daptomycin against Multidrug Resistant Staphylococcus aureusen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dash.depositing.authorJayamani, Elamparithien_US
dc.date.available2015-07-13T18:47:23Z
dc.identifier.doi10.1371/journal.pone.0128576*
dash.contributor.affiliatedConery, Annie
dash.contributor.affiliatedJayamani, Elamparithi
dash.contributor.affiliatedAusubel, Frederick


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