The heterotrimeric G-protein beta subunit Gpb1 controls hyphal growth under low oxygen conditions through the protein kinase A pathway and is essential for virulence in the fungus Mucor circinelloides.

Journal Article (Journal Article)

Mucor circinelloides, a dimorphic opportunistic pathogen, expresses three heterotrimeric G-protein beta subunits (Gpb1, Gpb2 and Gpb3). The Gpb1-encoding gene is up-regulated during mycelial growth compared with that in the spore or yeast stage. gpb1 deletion mutation analysis revealed its relevance for an adequate development during the dimorphic transition and for hyphal growth under low oxygen concentrations. Infection assays in mice indicated a phenotype with considerably reduced virulence and tissue invasiveness in the deletion mutants (Δgpb1) and decreased host inflammatory response. This finding could be attributed to the reduced filamentous growth in animal tissues compared with that of the wild-type strain. Mutation in a regulatory subunit of cAMP-dependent protein kinase A (PKA) subunit (PkaR1) resulted in similar phenotypes to Δgpb1. The defects exhibited by the Δgpb1 strain were genetically suppressed by pkaR1 overexpression, indicating that the PKA pathway is controlled by Gpb1 in M. circinelloides. Moreover, during growth under low oxygen levels, cAMP levels were much higher in the Δgpb1 than in the wild-type strain, but similar to those in the ΔpkaR1 strain. These findings reveal that M. circinelloides possesses a signal transduction pathway through which the Gpb1 heterotrimeric G subunit and PkaR1 control mycelial growth in response to low oxygen levels.

Full Text

Duke Authors

Cited Authors

  • Valle-Maldonado, MI; Patiño-Medina, JA; Pérez-Arques, C; Reyes-Mares, NY; Jácome-Galarza, IE; Ortíz-Alvarado, R; Vellanki, S; Ramírez-Díaz, MI; Lee, SC; Garre, V; Meza-Carmen, V

Published Date

  • October 2020

Published In

Volume / Issue

  • 22 / 10

Start / End Page

  • e13236 -

PubMed ID

  • 32562333

Electronic International Standard Serial Number (EISSN)

  • 1462-5822

International Standard Serial Number (ISSN)

  • 1462-5814

Digital Object Identifier (DOI)

  • 10.1111/cmi.13236


  • eng