Characterization of a heme-protein responsive to hypoxia in Paracoccidioides brasiliensis
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2020
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Oxygen is fundamental to the life of aerobic organisms and is not always available to Paracoccidioides cells.
During the life cycle stages, reduced oxygen levels directly affect general metabolic processes and oxygen
adaptation mechanisms may play a fundamental role on fungal ability to survive under such condition. Heme
proteins can bind to oxygen and participate in important biological processes. Several fungi, including
Paracoccidioides, express a heme-binding globin (fungoglobin - FglA) presumable to regulate fungal adaptation to
hypoxia. However, the characterization of fungoglobin in Paracoccidioides spp. has not yet been performed. In
this study, we predicted the structure of fungoglobin and determined its level of expression during hypoxic mimetic conditions. Genomic screening revealed that the fungoglobin gene is conserved in all species of the
Paracoccidioides genus. Molecular modeling showed biochemical and biophysical characteristics that support the
hypothesis that FglA binds to the heme group and oxygen as well. The fungoglobin transcript and proteins are
expressed at higher levels at the early treatment time, remaining elevated while oxygen is limited. A P. brasi liensis fglA knockdown strain depicted reduced growth in hypoxia indicating that this protein can be essential for
growth at low oxygen. Biochemical analysis confirmed the binding of fungoglobin to heme. Initial analyzes were
carried out to establish the relationship between FlglA and iron metabolism. The FglA transcript was up regu lated in pulmonary infection, suggesting its potential role in the disease establishment. We believe that this study
can contribute to the understanding of fungal biology and open new perspectives for scientific investigations.
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Oxygen, Iron deprivation, Fungoglobin, Paracoccidioidomycosis, Murine lung infection
Citação
OLIVEIRA, Lucas Nojosa et al. Characterization of a heme-protein responsive to hypoxia in Paracoccidioides brasiliensis. Fungal Genetics and Biology, Amsterdam, v. 144, e103446, 2020. DOI: 10.1016/j.fgb.2020.103446. Disponível em: https://www.sciencedirect.com/science/article/pii/S1087184520301377?via%3Dihub. Acesso em: 22 nov. 2024.