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dc.contributor.authorSoare, Alexandra
dc.date.accessioned2024-02-02T16:51:42Z
dc.date.available2024-02-02T16:51:42Z
dc.date.issued2023
dc.identifier.urihttp://hdl.handle.net/10713/21351
dc.descriptionUniversity of Maryland, Baltimore, School of Medicine, Ph.D., 2023en_US
dc.description.abstractMucormycosis is classified by NIAID as an emerging disease and is caused by Mucorales fungi. The recent surge of mucormycosis cases among COVID-19 patients has thrust the disease and lack of available treatments into the spotlight. Clinical data suggests a lack of inflammatory responses during mucormycosis despite severe fungal angioinvasion and tissue necrosis. In this dissertation, I sought to characterize immune evasion mechanisms by Mucorales, focusing on the interaction between fungi and macrophages. Macrophages infected with Mucorales fungi block the production of nitric oxide, a free radical molecule with strong antimicrobial properties and an important signaling role in immunity. Despite the increased expression of Nos2 mRNA and inducible nitric oxide synthase (iNOS) protein in Mucorales-infected macrophages, these macrophages are unable to produce nitric oxide, even when stimulated with nitric oxide-producing stimuli (LPS and IFN-γ). My results suggest that Mucorales fungi prevent the accumulation of nitric oxide through at least 2 mechanisms: (1) removal of nitric oxide from the surrounding environment, and (2) depletion of nutrients required to make nitric oxide. Additionally, a potent nitric oxide-donor (DETA-NONOate) inhibits in vitro growth of Mucorales fungi indicating that nitric oxide may be have antifungal activity against Mucorales. At lower concentrations of DETA-NONOate that are unable to inhibit growth of Mucorales, I observed downregulation of mRNAs encoding Mucorales virulence proteins including Mucoricin, a ricin-like toxin that is critical for Mucorales pathogenesis. By downregulating these genes, nitric oxide could be attenuating the virulence potential of the fungus, rendering it less pathogenic. My research describes a new immune evasion mechanism by Mucorales fungi and presents nitric oxide as a potential therapeutic for mucormycosis.en_US
dc.language.isoen_USen_US
dc.subject.meshFungien_US
dc.subject.meshMacrophagesen_US
dc.subject.meshMucoralesen_US
dc.subject.meshMucormycosisen_US
dc.subject.meshNitric Oxideen_US
dc.subject.meshRhizopusen_US
dc.titleNitric Oxide in Mucormycosis Pathogenesisen_US
dc.typedissertationen_US
dc.date.updated2024-02-01T02:05:42Z
dc.language.rfc3066en
dc.contributor.advisorBruno, Vincent, Ph.D.


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