Abstract
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 Debaryomyces hansenii (Dh) strains isolated from a wide variety of cheeses were identified as producing killer toxins active against Candida albicans and Candida tropicalis. We have analyzed the killer activity of these toxins in C. albicans mutants defective in MAPK signaling pathways and found that the lack of the MAPK Hog1 (but not Cek1 or Mkc1) renders cells hypersensitive to Dh 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 HOG1 gene showed that both activities were relevant for the survival of C. albicans to Dh 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 D. hansenii 242 strain (Dh-242) induced a slight intracellular increase in Reactive Oxygen Species (ROS), overexpression of cytosolic catalase did not protect C. albicans 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 Dh-242 killer toxin and resistance to Congo red, suggesting cell wall specific alterations in sensitive strains.
Highlights
Killer toxins or mycocins are yeastproteins with a toxic effect against other sensitive yeasts
The killer activity of seven of the D. hansenii mycocin-producing strains from Banjara’s work was tested against signal transduction C. albicans mutants in order to understand their mechanism of action. We show how these toxins have an increased action on specific Mitogen Activated Protein Kinase (MAPK) mutants but not others suggesting a role for the HOG MAPK in killer toxin resistance in C. albicans
Debaryomyces hansenii strains previously reported to have anticandida activity (Banjara et al, 2016) were tested against the C. albicans SC5314 strain at different pHs and temperatures (Table 4 and Supplementary Figure 1)
Summary
Killer toxins or mycocins are yeast (glyco)proteins with a toxic effect against other sensitive yeasts. A new killer toxin from wine maker S. cerevisiae strains, named Klus, was reported to kill all other mycocin producing S. cerevisiae strains (Rodríguez-Cousiño et al, 2011). Killer toxins are not exclusive to S. cerevisiae and other yeast genera such as Candida, Cryptococcus, Debaryomyces, Hansenula, Pichia, Abbreviations: MAPK, Mitogen Activated Protein Kinase. Killer toxins are protease-sensitive proteins, most of them only stable and active at acidic pH and low temperatures, losing activity above 35◦C and a pH above 6. Kluyveromyces lactis produces a zymocin with tRNase activity (Jablonowski and Schaffrath, 2007) and Hansenula mrakii HM1 inhibits the beta-1,3-glucan synthase activity perturbing bud formation and conjugation in yeasts (Takasuka et al, 1995)
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