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 fungusMucor circinelloides
Authors:
- Marco Iván Valle‐MaldonadoMVMarco Iván Valle‐Maldonado
- José Alberto Patiño‐MedinaJPJosé Alberto Patiño‐Medina
- Carlos Pérez‐ArquesCPCarlos Pérez‐Arques
- Rafael Ortíz‐AlvaradoRORafael Ortíz‐Alvarado
- Sandeep VellankiSVSandeep Vellanki
- Martha Isela Ramírez‐DíazMRMartha Isela Ramírez‐Díaz
- Soo Chan LeeSLSoo Chan Lee
- Victoriano GarreVictoriano Garre
- Víctor Meza‐CarmenVMVíctor Meza‐Carmen
Open Access
- 19 June 2020
- journal article
- research article
- Published by Wiley in Cellular Microbiology
- Vol. 22 (10) , e13236
Abstract
Mucor circinelloides , a dimorphic opportunistic pathogen, expresses three heterotrimeric G‐protein beta subunits (Gpb1, Gpb2, Gpb3). The Gpb1‐encoding gene is upregulated 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.Keywords
Funding Information
- Secretaría de Ciencia, Humanidades, Tecnología e Innovación (CB‐ 2011‐01‐167071)
- Coordinación de la Investigación Científica (2.36)
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