Inhibition of protein kinase A affects Paracoccidioides lutzii dimorphism
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2018
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Resumo
A critical step in the lifecycle of many fungal pathogens is the ability to switch between filamentous and yeast
growth, a process known as dimorphism. cAMP-dependent protein kinase (PKA) controls morphological changes
and the pathogenicity of several animal and plant pathogenic fungi. In this work, we report the analysis of PKA
activity during the mycelium to yeast transition in the pathogenic fungus Paracoccidioides lutzii. This fungus, as
well as the closely related species Paracoccidioides brasiliensis, causes paracoccidioidomycosis, a systemic mycosis
that affects thousands of people in Latin America. Infection occurs when hypha fragments or spores released from
mycelium are inhaled by the host, an event that triggers the morphological switch. We show here that PKA ac tivity is regulated in the fungus phase, increasing during the mycelium to yeast transition. Also, morphological
transition from mycelium to yeast is blocked by the compound H89, a specific PKA inhibitor. Nevertheless, the
fungus recovers its ability to change morphology when H89 is removed from the culture media. This recovery
is accompanied by a significant increase in PKA activity. Our results strongly indicate that PKA directly affects
phase transition in P. lutzii.
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Paracoccidioides lutzii, PKA, H89
Citação
SESTARI, Sheila J. et al . Inhibition of protein kinase a affects Paracoccidioides lutzii dimorphism. International Journal of Biological Macromolecules, Amsterdam, v. 113, 6, p. 1214-1220, 2018. DOI: 10.1016/j.ijbiomac.2018.03.023. Disponível em: https://www.sciencedirect.com/science/article/pii/S0141813017329562?via%3Dihub. Acesso em: 22 nov. 2024.