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Characterization of a heme-protein responsive to hypoxia in Paracoccidioides brasiliensis. | LitMetric

AI Article Synopsis

  • * Researchers predicted the structure of FglA and found that its gene is conserved across all Paracoccidioides species, with higher levels of expression during hypoxia, suggesting its significance for fungal survival.
  • * A knockdown of FglA in P. brasiliensis resulted in reduced growth under low oxygen, indicating its essential role, while also suggesting a link between FglA and iron metabolism, with implications for understanding fungal infections.

Article Abstract

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. brasiliensis 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 regulated 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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Source
http://dx.doi.org/10.1016/j.fgb.2020.103446DOI Listing

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