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dc.contributor.authorChileveru, Haritha Reddy
dc.contributor.authorLim, Shion A.
dc.contributor.authorChairatana, Phoom
dc.contributor.authorWommack, Andrew
dc.contributor.authorChiang, I-Ling
dc.contributor.authorNolan, Elizabeth Marie
dc.date.accessioned2016-08-30T16:23:59Z
dc.date.available2016-08-30T16:23:59Z
dc.date.issued2015-02
dc.date.submitted2015-02
dc.identifier.issn0006-2960
dc.identifier.issn1520-4995
dc.identifier.urihttp://hdl.handle.net/1721.1/104065
dc.description.abstractHuman α-defensin 5 (HD5) is a 32-residue cysteine-rich host-defense peptide that exhibits broad-spectrum antimicrobial activity and contributes to innate immunity in the human gut and other organ systems. Despite many years of investigation, its antimicrobial mechanism of action remains unclear. In this work, we report that HD5[subscript ox], the oxidized form of this peptide that exhibits three regiospecific disulfide bonds, causes distinct morphological changes to Escherichia coli and other Gram-negative microbes. These morphologies include bleb formation, cellular elongation, and clumping. The blebs are up to ∼1 μm wide and typically form at the site of cell division or cell poles. Studies with E. coli expressing cytoplasmic GFP reveal that HD5[subscript ox] treatment causes GFP emission to localize in the bleb. To probe the cellular uptake of HD5[subscript ox] and subsequent localization, we describe the design and characterization of a fluorophore–HD5 conjugate family. By employing these peptides, we demonstrate that fluorophore–HD5[subscript ox] conjugates harboring the rhodamine and coumarin fluorophores enter the E. coli cytoplasm. On the basis of the fluorescence profiles, each of these fluorophore–HD5[subscript ox] conjugates localizes to the site of cell division and cell poles. These studies support the notion that HD5[subscript ox'], at least in part, exerts its antibacterial activity against E. coli and other Gram-negative microbes in the cytoplasm.en_US
dc.description.sponsorshipUnited States. Army Research Office. Institute for Soldier Nanotechnologies (Contract W911NF-13-D-0001)en_US
dc.description.sponsorshipNational Science Foundation (U.S.) (Grant 007031)en_US
dc.description.sponsorshipMassachusetts Institute of Technology (MIT UROP Program funds)en_US
dc.description.sponsorshipRoyal Thai Government (RTG) (Fellowship)en_US
dc.description.sponsorshipMassachusetts Institute of Technology (2014 Richard R. Schrock summer graduate fellowship)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (NIH Office of the Director, grant DP2OD007045)en_US
dc.language.isoen_US
dc.publisherAmerican Chemical Society (ACS)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1021/bi501483qen_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourceProf. Nolan via Erja Kajosaloen_US
dc.titleVisualizing Attack of Escherichia coli by the Antimicrobial Peptide Human Defensin 5en_US
dc.typeArticleen_US
dc.identifier.citationChileveru, Haritha R., Shion A. Lim, Phoom Chairatana, Andrew J. Wommack, I-Ling Chiang, and Elizabeth M. Nolan. “ Visualizing Attack of Escherichia Coli by the Antimicrobial Peptide Human Defensin 5 .” Biochemistry 54, no. 9 (March 10, 2015): 1767-1777.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemistryen_US
dc.contributor.approverNolan, Elizabeth Marieen_US
dc.contributor.mitauthorChileveru, Haritha Reddyen_US
dc.contributor.mitauthorLim, Shion A.en_US
dc.contributor.mitauthorChairatana, Phoomen_US
dc.contributor.mitauthorWommack, Andrewen_US
dc.contributor.mitauthorChiang, I-Lingen_US
dc.contributor.mitauthorNolan, Elizabeth Marieen_US
dc.relation.journalBiochemistryen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0002-2515-5901
dc.identifier.orcidhttps://orcid.org/0000-0002-6153-8803
dc.identifier.orcidhttps://orcid.org/0000-0002-5356-3638
mit.licensePUBLISHER_POLICYen_US


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