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Article

Base Excision Repair AP-Endonucleases-Like Genes Modulate DNA Damage Response and Virulence of the Human Pathogen Cryptococcus neoformans

by
Rayssa Karla de Medeiros Oliveira
1,
Fabián Andrés Hurtado
1,
Pedro Henrique Gomes
1,
Luiza Lassi Puglia
1,
Fernanda Fonsêca Ferreira
2,
Kunal Ranjan
2,
Patrícia Albuquerque
3,
Márcio José Poças-Fonseca
2,*,†,
Ildinete Silva-Pereira
1,*,† and
Larissa Fernandes
3,*,†
1
Department of Cell Biology, Institute of Biological Sciences, University of Brasília, Brasília 70.910-900, Brazil
2
Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasília, Brasília 70.910-900, Brazil
3
Faculty of Ceilândia, University of Brasília, Brasília 72.220-275, Brazil
*
Authors to whom correspondence should be addressed.
†
These authors share the senior authorship.
J. Fungi 2021, 7(2), 133; https://doi.org/10.3390/jof7020133
Submission received: 23 December 2020 / Revised: 29 January 2021 / Accepted: 5 February 2021 / Published: 12 February 2021
(This article belongs to the Section Fungal Genomics, Genetics and Molecular Biology)
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Abstract

Pathogenic microbes are exposed to a number of potential DNA-damaging stimuli during interaction with the host immune system. Microbial survival in this situation depends on a fine balance between the maintenance of DNA integrity and the adaptability provided by mutations. In this study, we investigated the association of the DNA repair response with the virulence of Cryptococcus neoformans, a basidiomycete that causes life-threatening meningoencephalitis in immunocompromised individuals. We focused on the characterization of C. neoformansAPN1 and APN2 putative genes, aiming to evaluate a possible role of the predicted Apurinic/apyrimidinic (AP) endonucleases 1 and 2 of the base excision repair (BER) pathway on C. neoformans response to stress conditions and virulence. Our results demonstrated the involvement of the putative AP-endonucleases Apn1 and Apn2 in the cellular response to DNA damage induced by alkylation and by UV radiation, in melanin production, in tolerance to drugs and in virulence of C. neoformans in vivo. We also pointed out the potential use of DNA repair inhibitor methoxy-amine in combination with conventional antifungal drugs, for the development of new therapeutic approaches against this human fungal pathogen. This work provides new information about the DNA damage response of the highly important pathogenic fungus C. neoformans.
Keywords: Cryptococcus neoformans; base excision repair; AP-endonucleases-like genes; APN1 and APN2; virulence Cryptococcus neoformans; base excision repair; AP-endonucleases-like genes; APN1 and APN2; virulence

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MDPI and ACS Style

Oliveira, R.K.d.M.; Hurtado, F.A.; Gomes, P.H.; Puglia, L.L.; Ferreira, F.F.; Ranjan, K.; Albuquerque, P.; Poças-Fonseca, M.J.; Silva-Pereira, I.; Fernandes, L. Base Excision Repair AP-Endonucleases-Like Genes Modulate DNA Damage Response and Virulence of the Human Pathogen Cryptococcus neoformans. J. Fungi 2021, 7, 133. https://doi.org/10.3390/jof7020133

AMA Style

Oliveira RKdM, Hurtado FA, Gomes PH, Puglia LL, Ferreira FF, Ranjan K, Albuquerque P, Poças-Fonseca MJ, Silva-Pereira I, Fernandes L. Base Excision Repair AP-Endonucleases-Like Genes Modulate DNA Damage Response and Virulence of the Human Pathogen Cryptococcus neoformans. Journal of Fungi. 2021; 7(2):133. https://doi.org/10.3390/jof7020133

Chicago/Turabian Style

Oliveira, Rayssa Karla de Medeiros, Fabián Andrés Hurtado, Pedro Henrique Gomes, Luiza Lassi Puglia, Fernanda Fonsêca Ferreira, Kunal Ranjan, Patrícia Albuquerque, Márcio José Poças-Fonseca, Ildinete Silva-Pereira, and Larissa Fernandes. 2021. "Base Excision Repair AP-Endonucleases-Like Genes Modulate DNA Damage Response and Virulence of the Human Pathogen Cryptococcus neoformans" Journal of Fungi 7, no. 2: 133. https://doi.org/10.3390/jof7020133

APA Style

Oliveira, R. K. d. M., Hurtado, F. A., Gomes, P. H., Puglia, L. L., Ferreira, F. F., Ranjan, K., Albuquerque, P., Poças-Fonseca, M. J., Silva-Pereira, I., & Fernandes, L. (2021). Base Excision Repair AP-Endonucleases-Like Genes Modulate DNA Damage Response and Virulence of the Human Pathogen Cryptococcus neoformans. Journal of Fungi, 7(2), 133. https://doi.org/10.3390/jof7020133

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