AUTHOR=Morales-Menchén Ana , Navarro-García Federico , Guirao-Abad José P. , Román Elvira , Prieto Daniel , Coman Ioana V. , Pla Jesús , Alonso-Monge Rebeca 

TITLE=Non-canonical Activities of Hog1 Control Sensitivity of Candida albicans to Killer Toxins From Debaryomyces hansenii

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=8

YEAR=2018

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2018.00135

DOI=10.3389/fcimb.2018.00135

ISSN=2235-2988

ABSTRACT=<p>Certain yeasts secrete peptides known as killer toxins or mycocins with a deleterious effect on sensitive yeasts or filamentous fungi, a common phenomenon in environmental species. In a recent work, different <italic>Debaryomyces hansenii</italic> (<italic>Dh</italic>) strains isolated from a wide variety of cheeses were identified as producing killer toxins active against <italic>Candida albicans</italic> and <italic>Candida tropicalis</italic>. We have analyzed the killer activity of these toxins in <italic>C. albicans</italic> mutants defective in MAPK signaling pathways and found that the lack of the MAPK Hog1 (but not Cek1 or Mkc1) renders cells hypersensitive to <italic>Dh</italic> mycocins while mutants lacking other upstream elements of the pathway behave as the wild type strain. Point mutations in the phosphorylation site (T174A-176F) or in the kinase domain (K52R) of <italic>HOG1</italic> gene showed that both activities were relevant for the survival of <italic>C. albicans</italic> to <italic>Dh</italic> killer toxins. Moreover, Hog1 phosphorylation was also required to sense and adapt to osmotic and oxidative stress while the kinase activity was somehow dispensable. Although the addition of supernatant from the killer toxin- producing <italic>D. hansenii</italic> 242 strain (<italic>Dh</italic>-242) induced a slight intracellular increase in Reactive Oxygen Species (ROS), overexpression of cytosolic catalase did not protect <italic>C. albicans</italic> against this mycocin. This supernatant induced an increase in intracellular glycerol concentration suggesting that this toxin triggers an osmotic stress. We also provide evidence of a correlation between sensitivity to <italic>Dh</italic>-242 killer toxin and resistance to Congo red, suggesting cell wall specific alterations in sensitive strains.</p>