Pathogenic Yeast: Cryptococcus Neoformans

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Introduction

Cryptococcus neoformans is a pathogenic yeast found in soil, plants, and animals. In humans infection occurs via inhalation and deposition of spores in the lungs, in most cases. In healthy people, infection will trigger an immune response via alveolar macrophages or dendritic cells. This leads to restriction of the pathogens to benign granulomas. Exposure to Cryptococcus neoformans leads to disease in immunocompromised patients and it can be fatal. Indeed, there is a high incidence of death in HIV patients who develop pneumonia and meningitis following infection. The administration of antifungal drugs in these cases has proven ineffective. In infected tissues, Cryptococcus neoformans reside in acidic phagosomes, which are beneficial for its replication [1].

Cryptococcus neoformans scavenges for heme inside of its host using several methods. In conditions of low iron, Cryptococcus neoformans upregulates its CIG1 gene, which encodes a mannoprotein, Cig1, the pathogen uses to uptake iron. Cig1 binds to heme and traffics it to the membrane where it is endocytosed. The endocytosed heme is further processed in the fungal vacuole. Loss of Cig1 has been show to result in delayed growth of Cryptococcus neoformans [2]. Another pathogen that has been shown to scavenge for heme is African trypanosome.

Sleeping sickness, also known as Human African Trypanosomiasis, is a deadly disease, which is prevalent in Africa. It is transmitted by the tsetse fly. A bite from an infected fly will transfer two causative parasites to humans. The parasites are T.b. gambiense and T.b. rhodesiense, two subspecies of Trypanosoma brucei brucei. T.b. gambiense and T.b. rhodesiense can cause lasting infections due to the fact that they do not enter...

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... Hpr in the pathogen. Score sections for pathogen infectivity using an anti-Cryptococcus neoformans antibody. Determine survival rates in matched experimental and control groups by plotting Kaplan-Meier curves.

Interpretation

The pull-down assay would show that TLF1 complexes with both Hpr and Hb as predicted or not. Co-localization of TLF and Hpr in Cryptococcus neoformans by immunofluorescence would show endocytosis or not. Determination of survival rates in matched control and experimental groups would show whether TLF increases survival in iron-deficient SCID mice or not. Positive results in all cases would support the hypothesis.

Limitations

The use of multiple copies of the APOL1 gene does not mimic normal cellular conditions. The results obtained by using the SCID mice as model limits the translatability of the results to immunosuppressed humans.

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