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Published on: March 12, 2015
Cryptococcus neoformans and Cryptococcus gattii genes preferentially expressed during rat macrophage infection
Letícia Goulart1, Lívia Kmetzsch Rosa e Silva, Laura Chiapello
1Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Abstract:
Cryptococcus neoformans and Cryptococcus gattii are encapsulated yeast agents of cryptococcosis and facultative intracellular pathogens. The interaction of these yeasts with macrophages is essential for containing the infection. However, Cryptococcus spp. overcome this initial host defense barrier using a unique pathogenic strategy involving intracellular replication and cytoplasmic accumulation of polysaccharide-containing vesicles. Here, we employed representational difference analysis (RDA) to identify C. neoformans and C. gattii genes differentially expressed during intracellular growth in rat peritoneal macrophages. The upregulated transcripts of C. neoformans during macrophage interaction were related to ATP-binding cassette (ABC) transporters, intra-golgi transport, chaperone activity, ribosomal maintenance, NAD metabolism, histone methylation, stress response, and monosaccharide metabolism. In contrast, with C. gattii, upregulated genes were associated with cell growth, aerobic respiration, protein binding, microtubule nucleation, monosaccharides and nitrogen metabolism, inositol or phosphatidylinositol phosphatase activity, cellular signaling, and stress response. Our findings reveal new genes that may be necessary for the intracellular parasitism of C. neoformans and C. gattii.
Insights
This study identifies genes in Cryptococcus neoformans and Cryptococcus gattii that are upregulated during macrophage infection. These findings reveal potential new targets for understanding and combating cryptococcosis.
Area of Science:
- Mycology
- Infectious Diseases
- Cell Biology
Background:
- Cryptococcus neoformans and Cryptococcus gattii are fungal pathogens causing cryptococcosis.
- These yeasts are facultative intracellular pathogens that interact with macrophages, a key host defense mechanism.
- Cryptococcus species evade host defenses through intracellular replication and vesicle accumulation.
Purpose of the Study:
- To identify genes differentially expressed by C. neoformans and C. gattii during intracellular growth within macrophages.
- To uncover novel genetic factors contributing to the intracellular parasitism of these fungi.
Main Methods:
- Representational difference analysis (RDA) was used to compare gene expression profiles.
- Gene expression was analyzed during the intracellular growth phase in rat peritoneal macrophages.
Main Results:
- Upregulated genes in C. neoformans included those involved in ABC transporters, intra-Golgi transport, and metabolism.
- Upregulated genes in C. gattii were associated with cell growth, respiration, signaling, and metabolism.
- Distinct sets of genes were identified for each species during intracellular macrophage growth.
Conclusions:
- The study identified novel genes potentially crucial for the intracellular survival and virulence of C. neoformans and C. gattii.
- These findings offer new insights into the pathogenic strategies of Cryptococcus species within host macrophages.
