Open AccessThe 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
Author(s) -
ValleMaldonado Marco Iván,
PatiñoMedina José Alberto,
PérezArques Carlos,
ReyesMares Nancy Yadira,
JácomeGalarza Irvin Eduardo,
OrtízAlvarado Rafael,
Vellanki Sandeep,
RamírezDíaz Martha Isela,
Lee Soo Chan,
Garre Victoriano,
MezaCarmen Víctor
Publication year - 2020
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.13236
Subject(s) - heterotrimeric g protein , biology , mucor circinelloides , protein subunit , mutant , protein kinase a , virulence , fungal protein , signal transduction , microbiology and biotechnology , kinase , biochemistry , g protein , mucor , gene , aspergillus
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 (Δ gpb1 ) 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 Δ gpb1 . The defects exhibited by the Δ gpb1 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 Δ gpb1 than in the wild‐type strain, but similar to those in the Δ pkaR1 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.