Date of Award

1-1-2019

Language

English

Document Type

Master's Thesis

Degree Name

Master of Science (MS)

College/School/Department

Department of Biomedical Sciences

Content Description

1 online resource (viii, 64 pages) : illustrations (some color)

Dissertation/Thesis Chair

Magdia De Jesus

Committee Members

Sudha Chatuverdi, Nicholas Mantis

Keywords

Candida auris, Histopathology, Neutropenia, qPCR, Candidiasis, Mycoses, Mice as laboratory animals, Mice, Laboratories

Subject Categories

Biology

Abstract

In less than a decade, the emerging fungal pathogen Candida auris has become a major public health threat due to its multidrug resistant (MDR) phenotype, high transmissibility, and high mortality rates that range between 30%-60%. Unlike other Candida species, C. auris has acquired high levels of resistance to an already limited arsenal of antifungals. As an emerging pathogen, there are currently a limited number of documented murine models of C. auris infection. These animal models using a range of inoculums from 105 –108 cells per mouse, and the environmental and occupational exposure of working with these models has not been clearly defined. In order to establish an animal model of infection for C. auris, the biosafety and biosecurity of the researchers and animal caretakers had to be assessed. We established four important practices that included proper personal protection equipment (PPE), a buddy system, disinfection and biomonitoring of surfaces. These practices were important for the containment of C. auris infection as our studies determined that shedding of the organism is dose-dependent. Due to the limited animal models for sustained C. auris infections, we compared two mouse models that achieve a compromised immunity by depleting neutrophils using 1A8, anti-Ly6G+ and RB6-8C5, anti- Ly6G+- Ly6C+ monoclonal antibodies when administered IP every 48 hours. Our study determined that using an intravenous infection of 107 C. auris cells leads to a high fungal burden in the kidney, heart and brain while the gavage model does not provide evidence of dissemination. The study also revealed that an infection of 108 is fatal in both neutropenic models, regardless of which antibody was used for neutrophil-depletion. We also observed that between 8-13 days post C. auris infection, mice displayed a unique behavioral phenotype characterize by torticollis and tail spinning when elevated and that this phenotype can progress to head bobbing and body curling by day 21 post-infection.

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