Characterization of the Paracoccidioides hypoxia response reveals new insights into pathogenesis mechanisms of this important human pathogenic fungus
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2015
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Hypoxic microenvironments are generated during fungal infection. It has been described
that to survive in the human host, fungi must also tolerate and overcome in vivo microenvironmental
stress conditions including low oxygen tension; however nothing is known how
Paracoccidioides species respond to hypoxia. The genus Paracoccidioides comprises
human thermal dimorphic fungi and are causative agents of paracoccidioidomycosis
(PCM), an important mycosis in Latin America.
Methodology/Principal Findings:
In this work, a detailed hypoxia characterization was performed in Paracoccidioides. Using
NanoUPLC-MSE proteomic approach, we obtained a total of 288 proteins differentially regulated
in 12 and 24 h of hypoxia, providing a global view of metabolic changes during this
stress. In addition, a functional characterization of the homologue to the most important molecule
involved in hypoxia responses in other fungi, the SREBP (sterol regulatory element
binding protein) was performed. We observed that Paracoccidioides species have a functional
homologue of SREBP, named here as SrbA, detected by using a heterologous
genetic approach in the srbA null mutant in Aspergillus fumigatus. Paracoccidioides srbA
(PbsrbA), in addition to involvement in hypoxia, is probable involved in iron adaptation and
azole drug resistance responses. Conclusions/Significance:
In this study, the hypoxia was characterized in Paracoccidioides. The first results can be
important for a better understanding of the fungal adaptation to the host and improve the
arsenal of molecules for the development of alternative treatment options in future, since molecules related to fungal adaptation to low oxygen levels are important to virulence and
pathogenesis in human pathogenic fungi.
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LIMA, Patrícia de Sousa et. al. Characterization of the Paracoccidioides hypoxia response reveals new insights into pathogenesis mechanisms of this important human pathogenic fungus. PLoS Neglected Tropical Diseases, San Francisco, v. 9, n. 12, e0004282, 2015.