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The MAPK Hog1 mediates the response to amphotericin B in Candida albicans

José Pedro Guirao-Abad1, Ruth Sánchez-Fresneda2, Elvira Román3

  • 1Departamento de Microbiología y Parasitología, Facultad de Farmacia, Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS), Universidad Complutense de Madrid, Plaza de Ramón y Cajal s/n, E-28040 Madrid, Spain; Área de Microbiología, Facultad de Biología, Universidad de Murcia, E-30071 Murcia, Spain.

Fungal Genetics and Biology : FG & B
|November 23, 2019
PubMed

Insights

The Hog1 mitogen-activated protein kinase (MAPK) pathway is essential for Candida albicans survival during amphotericin B (AMB) treatment, as Hog1 phosphorylation and kinase activity are required to combat AMB-induced oxidative stress.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • The opportunistic fungal pathogen Candida albicans relies on stress response pathways for survival.
  • Amphotericin B (AMB), an antifungal polyene, induces oxidative stress in C. albicans.
  • The High Osmolarity Glycerol (HOG) mitogen-activated protein kinase (MAPK) pathway is a key stress response regulator.

Purpose of the Study:

  • To investigate the role of the MAPK Hog1 in sensing and surviving AMB-induced stress in C. albicans.
  • To determine the specific requirements of Hog1's kinase activity and phosphorylation for AMB resistance.

Main Methods:

  • Generation and characterization of hog1 null mutants and mutated Hog1 versions.
  • Assessment of C. albicans susceptibility to AMB using flow cytometry.
  • Measurement of intracellular reactive oxygen species (ROS) and trehalose accumulation.

Main Results:

  • Hog1-deficient mutants exhibit increased susceptibility to AMB.
  • AMB treatment leads to Hog1 phosphorylation, indicating its activation.
  • Both Hog1 kinase activity and phosphorylation are crucial for coping with AMB.
  • AMB induces ROS accumulation independently of Hog1, but rotenone treatment mitigates ROS and improves viability.
  • Trehalose synthesis is induced by AMB in a Hog1-independent manner.

Conclusions:

  • The MAPK Hog1 pathway is essential for C. albicans survival and adaptation to AMB treatment.
  • Hog1's function in AMB resistance is linked to its kinase activity and phosphorylation status.
  • AMB-induced oxidative stress is partially mediated by the electron transport chain and can be modulated by rotenone.
Keywords:
Amphotericin BAntifungalsCandida albicansHOG pathwayMAPK phosphorylationROS

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