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碱基切除修复类AP核酸内切酶基因调节人类病原体的DNA损伤反应和毒力

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

作者信息

Oliveira Rayssa Karla de Medeiros, Hurtado Fabián Andrés, Gomes Pedro Henrique, Puglia Luiza Lassi, Ferreira Fernanda Fonsêca, Ranjan Kunal, Albuquerque Patrícia, Poças-Fonseca Márcio José, Silva-Pereira Ildinete, Fernandes Larissa

机构信息

Department of Cell Biology, Institute of Biological Sciences, University of Brasília, Brasília 70.910-900, Brazil.

Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasília, Brasília 70.910-900, Brazil.

出版信息

J Fungi (Basel). 2021 Feb 12;7(2):133. doi: 10.3390/jof7020133.

DOI:10.3390/jof7020133
PMID:33673204
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7917787/
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 , a basidiomycete that causes life-threatening meningoencephalitis in immunocompromised individuals. We focused on the characterization of and 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 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 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 .

摘要

在与宿主免疫系统相互作用的过程中，致病微生物会暴露于多种潜在的DNA损伤刺激之下。在这种情况下，微生物的存活取决于DNA完整性的维持与突变所提供的适应性之间的精细平衡。在本研究中，我们调查了DNA修复反应与一种担子菌的毒力之间的关联，该担子菌可在免疫功能低下的个体中引发危及生命的脑膜脑炎。我们着重对该菌的两个假定基因进行了表征，旨在评估碱基切除修复（BER）途径中预测的脱嘌呤/脱嘧啶（AP）核酸内切酶1和2在应对应激条件及毒力方面可能发挥的作用。我们的结果表明，假定的AP核酸内切酶Apn1和Apn2参与了细胞对烷基化和紫外线辐射诱导的DNA损伤的反应、黑色素生成、对药物的耐受性以及该菌在体内的毒力。我们还指出了DNA修复抑制剂甲氧基胺与传统抗真菌药物联合使用在开发针对这种人类真菌病原体的新治疗方法方面的潜在用途。这项工作提供了有关这种极为重要的致病真菌的DNA损伤反应的新信息。

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