Please use this identifier to cite or link to this item: https://hdl.handle.net/1889/4301
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dc.contributor.advisorCampanini, Barbara-
dc.contributor.authorDe Bei, Omar-
dc.date.accessioned2021-04-22T17:12:44Z-
dc.date.available2021-04-22T17:12:44Z-
dc.date.issued2021-04-
dc.identifier.urihttps://hdl.handle.net/1889/4301-
dc.description.abstractThe Isd (Iron-regulated Surface Determinant) system of Staphylococcus aureus, together with siderophores, provides iron to sustain bacterial metabolism during colonization of the host. The system is composed of eight proteins that extract heme from hemoglobin (Hb), transfer it through the bacterial cell wall and membrane, and degrade the cofactor to retrieve iron. The project focuses on the complex between human Hb and IsdB, the cell-wall anchored protein in charge of binding Hb and remove heme. An isofunctional protein, IsdH, is also localized on the cell surface, but in vivo studies report that S. aureus relies especially on IsdB to infect the human host. This experimental evidence and the MRSA threat make IsdB a suitable target to develop new antimicrobial agents. Interference with protein-protein interactions poses new opportunities and challenges for the development of innovative therapeutics and requires an in-depth knowledge of biochemical details of protein complexes. The main aims of my Ph.D. project were the biochemical and biophysical characterization of IsdB-Hb interaction and heme extraction, and the validation of molecules identified by in silico screening as potential disruptors of the complex (in collaboration with Prof.ssa F. Spyrakis, Università di Torino). These protein-protein interaction inhibitors might in principle find application as first-in-class antimicrobials, cutting down the iron supply.en_US
dc.language.isoItalianoen_US
dc.publisherUniversità degli Studi di Parma. Dipartimento di Scienze degli alimenti e del farmacoen_US
dc.relation.ispartofseriesDottorato di ricerca in Scienze del farmaco, delle biomolecole e dei prodotti per la saluteen_US
dc.rights© Omar De Bei, 2021en_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internazionaleen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectHemophoresen_US
dc.subjectHemoglobinen_US
dc.subjectCryo-EMen_US
dc.subjectSPRen_US
dc.subjectSEC-MALSen_US
dc.subjectUV-Vis Spectroscopyen_US
dc.subjectSAXSen_US
dc.subjectELISAen_US
dc.subjectAntibioticsen_US
dc.subjectAMRen_US
dc.subjectMRSAen_US
dc.subjectS. auruesen_US
dc.titleComplex between S. aureus hemophore and human hemoglobin as a target for novel antimicrobial agents: from complex characterization to compounds identificationen_US
dc.typeDoctoral thesisen_US
dc.subject.miurBIO/10en_US
dc.subject.miurBIO/11en_US
Appears in Collections:Scienze del farmaco, delle biolomolecole e dei prodotti per la salute. Tesi di dottorato

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