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Biolistic Transformation of a Fluorescent Tagged Gene into the Opportunistic Fungal Pathogen Cryptococcus neoformans
Published on: March 19, 2015
Cryptococcus neoformans and gattii promote DNA damage in human peripheral blood mononuclear cells
Jéssica Cristina Bilizario Noguerol Andrade1, Mariana Gatto1, Daniela Ramos Rodrigues2
1Botucatu School of Medicine - UNESP, Campus Botucatu, Tropical Diseases Department, São Paulo, Brazil.
Abstract:
Cryptococcosis, a systemic mycosis capable of disseminating to the central nervous system with frequent lethal effects, is caused by the species Cryptococus neoformans and Cryptococcus gattii. Several infectious agents such as virus, bacteria, and parasites may be associated to DNA damage and carcinogenesis in humans. Products of the oxidative metabolism, such as NO, produced as a host defense mechanism to destroy these pathogens, have been implicated in this damage process, due to excessive production related to an established chronic inflammatory response. Here, we investigated whether C. neoformans and /or C. gattii can cause DNA damage in human peripheral blood mononuclear cells (PBMCs) and whether this process is related to NO levels produced by PBMCs. We found that both species are equally able to induce genotoxicity in PBMCs. However, an association between DNA damage and high NO levels was only detected in relation to C. gattii. The results point to the possibility that patients with cryptococcosis are more susceptible to the development of other diseases.
Insights
Both Cryptococcus neoformans and Cryptococcus gattii cause DNA damage in human cells. However, only Cryptococcus gattii infection showed a link between DNA damage and elevated nitric oxide (NO) levels.
Area of Science:
- Mycology
- Immunology
- Genetics
Background:
- Cryptococcosis, caused by Cryptococcus neoformans and Cryptococcus gattii, is a serious fungal infection.
- Infectious agents can induce DNA damage and cancer, partly due to oxidative stress from host defense mechanisms like nitric oxide (NO).
Purpose of the Study:
- To investigate if C. neoformans and C. gattii induce DNA damage in human peripheral blood mononuclear cells (PBMCs).
- To determine if this DNA damage is associated with NO production by PBMCs.
Main Methods:
- Exposure of human PBMCs to C. neoformans and C. gattii.
- Assessment of genotoxicity (DNA damage) in PBMCs.
- Measurement of nitric oxide (NO) levels in PBMCs.
Main Results:
- Both C. neoformans and C. gattii equally induced genotoxicity in PBMCs.
- A significant association between DNA damage and high NO levels was observed only with C. gattii.
Conclusions:
- C. neoformans and C. gattii can cause DNA damage in human PBMCs.
- Elevated NO levels are specifically linked to C. gattii-induced DNA damage.
- Patients with cryptococcosis may have increased susceptibility to other diseases due to DNA damage.
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