Abstract
The infection of Cryptococcus neoformans is acquired through the inhalation of desiccated yeast cells and basidiospores originated from the environment, particularly from bird’s droppings and decaying wood. Three environmental strains of C. neoformans originated from bird droppings (H4, S48B and S68B) and C. neoformans reference clinical strain (H99) were used for intranasal infection in C57BL/6 mice. We showed that the H99 strain demonstrated higher virulence compared to H4, S48B and S68B strains. To examine if gene expression contributed to the different degree of virulence among these strains, a genome-wide microarray study was performed to inspect the transcriptomic profiles of all four strains. Our results revealed that out of 7,419 genes (22,257 probes) examined, 65 genes were significantly up-or down-regulated in H99 versus H4, S48B and S68B strains. The up-regulated genes in H99 strain include Hydroxymethylglutaryl-CoA synthase (MVA1), Mitochondrial matrix factor 1 (MMF1), Bud-site-selection protein 8 (BUD8), High affinity glucose transporter 3 (SNF3) and Rho GTPase-activating protein 2 (RGA2). Pathway annotation using DAVID bioinformatics resource showed that metal ion binding and sugar transmembrane transporter activity pathways were highly expressed in the H99 strain. We suggest that the genes and pathways identified may possibly play crucial roles in the fungal pathogenesis.
Highlights
Over the last decade, opportunistic fungal pathogens such as Cryptococcus neoformans have become increasingly important due to AIDS pandemic and the emergence of drug resistant strains [1]
Mice infected with C. neoformans H99 strain were found dead starting from day 18, while the remaining of the mice infected with environmental strains survived throughout the end of observation period of 42 days (Fig 1A)
The fungal load in both lung and brain tissues was higher for mice infected with the H99 strain, comparing to those infected with the environmental strains (Fig 1B and 1C)
Summary
Opportunistic fungal pathogens such as Cryptococcus neoformans have become increasingly important due to AIDS pandemic and the emergence of drug resistant strains [1]. C. neoformans is an encapsulated yeast-like fungus which causes life-threatening diseases of the pulmonary and central nervous system. More than 900,000 cases of cryptococcal meningitis were reported each year, resulting in approximately 600,000 deaths worldwide [2]. Cryptococcal infection is acquired by the infectious propagules [3] derived from desiccated yeast cells and basidiospores from birds excreta and decaying wood [4, 5]. PLOS ONE | DOI:10.1371/journal.pone.0137457 September 11, 2015
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