student profile: Ms Kenya Fernandes


Thesis work

Thesis title: Phenotypic plasticity in Cryptococcus: clinical outcome and alternative antifungal therapy

Supervisors: Marc WILKINS, Dee CARTER

Thesis abstract:

Cryptococcosis, caused by the fungal pathogens Cryptococcus neoformans and the Cryptococcus gattii complex, poses a major threat to human health as one of the most frequently occurring and globally distributed fungal infections. The ability of Cryptococcus to produce variable cell morphologies during host infection has long been known, and recent genomic studies have emphasised the plasticity of the cryptococcal genome. This variation includes dramatic modulation of the size and structure of the capsule and cell body, as well as the production of variant populations of cells including giant cells (>15 µm), and micro cells (<1 µm). These phenotypes are frequently observed and are likely to play an important role in human infection. In the first part of this study, I will investigate variant phenotypes produced by Cryptococcus cells under stressful conditions and how these phenotypes compare between strains and species, what effect these phenotypes have on clinical outcome and antifungal susceptibility, and what effect exposure to antifungal drugs has on these phenotypes. Previous work in the Carter lab has shown that the multifunctional milk glycoprotein lactoferrin acts synergistically with amphotericin B against Cryptococcus, reducing its minimum inhibitory concentration substantially. This is significant as amphotericin B is quite toxic and its use requires hospitalisation, monitoring, and is associated with severe side effects. A wide spectrum of activity across yeasts and moulds have been reported for Lf and its derived peptides, some of which have potency surpassing that of the intact protein. However, considerable research is still required to understand the antifungal actions of these molecules, and their potential to support current antifungals such as AMB. In the second part of this study, I will investigate lactoferrin as a synergent to potentiate the effect of currently used antifungal drugs against Cryptococcus and other pathogenic yeasts through an evaluation of its antifungal spectrum of activity and an investigation of the mechanistic basis of antifungal action.

Note: This profile is for a student at the University of Sydney. Views presented here are not necessarily those of the University.