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dc.contributor.authorLeal Jr., Sixto M.
dc.contributor.authorRoy, Sanhita
dc.contributor.authorVareechon, Chairut
dc.contributor.authorJesús Carrión, Steven de
dc.contributor.authorClark, Heather
dc.contributor.authorSánchez López-Berges, M.
dc.contributor.authorDi Pietro, Antonio
dc.contributor.authorSchrettl, Marcus
dc.contributor.authorBeckmann, Nicola
dc.contributor.authorRedl, Bernhard
dc.contributor.authorHaas, Hubertus
dc.contributor.authorPearlman, Eric
dc.date.accessioned2017-12-12T12:00:24Z
dc.date.available2017-12-12T12:00:24Z
dc.date.issued2013
dc.identifier.urihttp://hdl.handle.net/10396/15710
dc.description.abstractFilamentous fungi are an important cause of pulmonary and systemic morbidity and mortality, and also cause corneal blindness and visual impairment worldwide. Utilizing in vitro neutrophil killing assays and a model of fungal infection of the cornea, we demonstrated that Dectin-1 dependent IL-6 production regulates expression of iron chelators, heme and siderophore binding proteins and hepcidin in infected mice. In addition, we show that human neutrophils synthesize lipocalin-1, which sequesters fungal siderophores, and that topical lipocalin-1 or lactoferrin restricts fungal growth in vivo. Conversely, we show that exogenous iron or the xenosiderophore deferroxamine enhances fungal growth in infected mice. By examining mutant Aspergillus and Fusarium strains, we found that fungal transcriptional responses to low iron levels and extracellular siderophores are essential for fungal growth during infection. Further, we showed that targeting fungal iron acquisition or siderophore biosynthesis by topical application of iron chelators or statins reduces fungal growth in the cornea by 60% and that dual therapy with the iron chelator deferiprone and statins further restricts fungal growth by 75%. Together, these studies identify specific host iron-chelating and fungal iron-acquisition mediators that regulate fungal growth, and demonstrate that therapeutic inhibition of fungal iron acquisition can be utilized to treat topical fungal infections.es_ES
dc.format.mimetypeapplication/pdfes_ES
dc.language.isoenges_ES
dc.publisherPublic Library of Sciencees_ES
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/4.0/es_ES
dc.sourcePLoS Pathogens 9(7): e1003436 (2013)es_ES
dc.subjectCorneaes_ES
dc.subjectFungal diseaseses_ES
dc.subjectAspergillus fumigatuses_ES
dc.subjectFungal growthes_ES
dc.subjectNeutrophilses_ES
dc.subjectStatinses_ES
dc.subjectEye diseaseses_ES
dc.subjectEyeses_ES
dc.titleTargeting Iron Acquisition Blocks Infection with the Fungal Pathogens Aspergillus fumigatus and Fusarium oxysporumes_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.relation.publisherversionhttp://dx.doi.org/10.1371/journal.ppat.1003436es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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