Establish a Galleria Mellonella Model for the Study of Coccidioides Infection and Virulence

dc.contributor.advisorHung, Chiung-Yu
dc.contributor.authorBarker, Matthew Mark
dc.contributor.committeeMemberYu, Jieh-Juen
dc.contributor.committeeMemberLee, Soo Chan
dc.creator.orcidhttps://orcid.org/0000-0001-9046-7699
dc.date.accessioned2024-01-25T22:33:46Z
dc.date.available2023-05-17
dc.date.available2024-01-25T22:33:46Z
dc.date.issued2021
dc.descriptionThis item is available only to currently enrolled UTSA students, faculty or staff. To download, navigate to Log In in the top right-hand corner of this screen, then select Log in with my UTSA ID.
dc.description.abstractCoccidioides immitis and Coccidioides posadasii are dimorphic fungal pathogens that can cause a life-threatening disease in both immunocompromised and healthy individuals. Mice are biologically similar to humans and they are commonly used for studies of virulence mechanisms and immune responses to Coccidioides infection, however, they are cost-prohibitory for high- content screening of potential drug candidates and genome-wide evaluation of fungal virulence factors. Galleria mellonella larvae have emerged as viable alternatives to several fungal infection models since they are economic, survive at 37 ºC and require no special growing equipment. This study aims to establish the infection criteria of Galleria mellonella larvae with Coccidioides spores. The larvae are challenged by the haemocoel route. Mortality, histopathology, fungal burden and melanization rate were monitored for a period of 7 days postchallenge. Results showed that Coccidioides spp. can convert to parasitic spherules in the haemocoel inoculation sites and the lethal dose (LD100) is ~5x10^5 viable spores of C. posadasii C735, a highly virulent isolate for mice. We further explored the application of this insect model to evaluate therapeutic efficacy of a well- known antifungal drug (i.e. amphotericin B) and to screen a mutant library of C. posadasii C735 for identification of attenuated strains. Results demonstrated that treatment with AmB could significantly prolong survival of the Coccidioides-infected larvae. We further identified 4 Coccidioides mutants that displayed various degree of reduction in melanization and mortality. Similarly, these mutants demonstrated reduced virulence in a murine model of pulmonary coccidioidomycosis. The findings suggest G. mellonella larvae may be a useful in vivo model of coccidioidomycosis and convenient as a pre-screening assay for identification of novel antifungal drugs and fungal virulence factors.
dc.description.departmentIntegrative Biology
dc.format.extent41 pages
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12588/2462
dc.languageen
dc.subjectCoccidioides
dc.subjectGalleria mellonella
dc.subject.classificationMicrobiology
dc.titleEstablish a Galleria Mellonella Model for the Study of Coccidioides Infection and Virulence
dc.typeThesis
dc.type.dcmiText
dcterms.accessRightspq_closed
thesis.degree.departmentIntegrative Biology
thesis.degree.grantorUniversity of Texas at San Antonio
thesis.degree.levelMasters
thesis.degree.nameMaster of Science

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