CoChat
Sign Up
Cited by 111Fungal and yeast genetics researchYeasts and Rust Fungi StudiesPlant and Fungal Interactions Research

The DOI matches its Crossref record; 193 of the 199 references it cites were found in a registry or an index.

The Biology of Pichia membranifaciens Killer Toxins

Open access
Belda, Ignacio, Ruiz, Javier, Alonso, Alejandro, Marquina, Domingo, Santos, Antonio·2017·Toxins
DOI 10.3390/toxins9040112PMC PMC5408186
Open this paper in CoChat — free accountOpen PDF

Abstract

The killer phenomenon is defined as the ability of some yeast to secrete toxins that are lethal to other sensitive yeasts and filamentous fungi. Since the discovery of strains of Saccharomyces cerevisiae capable of secreting killer toxins, much information has been gained regarding killer toxins and this fact has substantially contributed knowledge on fundamental aspects of cell biology and yeast genetics. The killer phenomenon has been studied in Pichia membranifaciens for several years, during which two toxins have been described. PMKT and PMKT2 are proteins of low molecular mass that bind to primary receptors located in the cell wall structure of sensitive yeast cells, linear (1→6)-β-d-glucans and mannoproteins for PMKT and PMKT2, respectively. Cwp2p also acts as a secondary receptor for PMKT. Killing of sensitive cells by PMKT is characterized by ionic movements across plasma membrane and an acidification of the intracellular pH triggering an activation of the High Osmolarity Glycerol (HOG) pathway. On the contrary, our investigations showed a mechanism of killing in which cells are arrested at an early S-phase by high concentrations of PMKT2. However, we concluded that induced mortality at low PMKT2 doses and also PMKT is indeed of an apoptotic nature. Killer yeasts and their toxins have found potential applications in several fields: in food and beverage production, as biocontrol agents, in yeast bio-typing, and as novel antimycotic agents. Accordingly, several applications have been found for P. membranifaciens killer toxins, ranging from pre- and post-harvest biocontrol of plant pathogens to applications during wine fermentation and ageing (inhibition of Botrytis cinerea, Brettanomyces bruxellensis, etc.).

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3390/toxins9040112

Cites

193 of 193 references verified0 citation errors · 0 not checkable

Statistics

Figures

Figure 1 Analysis of the transcriptional response of S. cerevisiae to PMKT. Genes, sorted into functional categories, induced after a PMKT exposure by more than 3-fold and repressed by more than two-fold.
Figure 1 Analysis of the transcriptional response of S. cerevisiae to PMKT. Genes, sorted into functional categories, induced after a PMKT exposure by more than 3-fold and repressed by more than two-fold.CC BY · PubMed Central
Figure 2 Cellular response to PMKT exposure deduced from the analysis of the transcriptional response of S. cerevisiae to the toxin. Once PMKT has reached the cell wall through an interaction with (1→6)-β-d-glucans, PMKT interacts with the cytoplasmic membrane through the interaction with cwp2p (not shown in the figure). This interaction, through a mechanism of unknown nature (?), leads to disruption of electrochemical gradients. Cellular receptors are not included in the scheme for simplification. PMKT cause the formation of unregulated channels through which cations and small metabolites (e.g., K+, H+, Na+, glycerol) flow. These changes in pHi, turgor or ionic concentrations generates a transcriptional response through the activation of Hog1p. Genes (CTT1, HSP12, HSP26, and DDR2), related with a general stress response, and genes (GPD1 and GPP2), involved in glycerol synthesis, are transcribed to compensate the toxic effects of PMKT. Cations and glycerol, among others, can leak out from sensitive cells generating cell death. Highlighted in a box are the induction levels of the most up-regulated genes. Abbreviations: DHAP (dihydroxyacetone phosphate), G3P (glycerol-3-phosphate), FBP (fructose-1,6-bisphosphate), MG (methylglyoxal), CoQ (coenzyme Q), S-LG (S-d-lactoylglutathione), GSH (glutathione).
Figure 2 Cellular response to PMKT exposure deduced from the analysis of the transcriptional response of S. cerevisiae to the toxin. Once PMKT has reached the cell wall through an interaction with (1→6)-β-d-glucans, PMKT interacts with the cytoplasmic membrane through the interaction with cwp2p (not shown in the figure). This interaction, through a mechanism of unknown nature (?), leads to disruption of electrochemical gradients. Cellular receptors are not included in the scheme for simplification. PMKT cause the formation of unregulated channels through which cations and small metabolites (e.g., K+, H+, Na+, glycerol) flow. These changes in pHi, turgor or ionic concentrations generates a transcriptional response through the activation of Hog1p. Genes (CTT1, HSP12, HSP26, and DDR2), related with a general stress response, and genes (GPD1 and GPP2), involved in glycerol synthesis, are transcribed to compensate the toxic effects of PMKT. Cations and glycerol, among others, can leak out from sensitive cells generating cell death. Highlighted in a box are the induction levels of the most up-regulated genes. Abbreviations: DHAP (dihydroxyacetone phosphate), G3P (glycerol-3-phosphate), FBP (fructose-1,6-bisphosphate), MG (methylglyoxal), CoQ (coenzyme Q), S-LG (S-d-lactoylglutathione), GSH (glutathione).CC BY · PubMed Central
Figure 3 Mechanisms of the killing activity of PMKT2 depending on toxin dosage. (A) High concentrations of PMKT2 caused cell cycle arrest at G1/S. Flow cytometry analyses of DNA content of S. cerevisiae revealed that cells treated with high doses of PMKT2 were arrested at an early S phase with a nascent bud. (B) Asynchronously growing cells exposed to inactivated toxin remained fully viable. (C) Cells treated with low concentrations of PMKT2 lead to the typical markers of apoptosis. Figure adapted and reproduced with permission (Santos et al. 2013) [42].
Figure 3 Mechanisms of the killing activity of PMKT2 depending on toxin dosage. (A) High concentrations of PMKT2 caused cell cycle arrest at G1/S. Flow cytometry analyses of DNA content of S. cerevisiae revealed that cells treated with high doses of PMKT2 were arrested at an early S phase with a nascent bud. (B) Asynchronously growing cells exposed to inactivated toxin remained fully viable. (C) Cells treated with low concentrations of PMKT2 lead to the typical markers of apoptosis. Figure adapted and reproduced with permission (Santos et al. 2013) [42].CC BY · PubMed Central
Figure 4 Transcriptional response of S. cerevisiae after exposure to pro-apoptotic concentrations of PMKT. Respiratory chain of S. cerevisiae with the indication of sites where ROS are formed and the main mitochondrial enzymes involved. Numbers indicate the levels of induction of some genes coding for such representative enzymes. Figure adapted and reproduced with permission (Santos et al. 2011) [74].
Figure 4 Transcriptional response of S. cerevisiae after exposure to pro-apoptotic concentrations of PMKT. Respiratory chain of S. cerevisiae with the indication of sites where ROS are formed and the main mitochondrial enzymes involved. Numbers indicate the levels of induction of some genes coding for such representative enzymes. Figure adapted and reproduced with permission (Santos et al. 2011) [74].CC BY · PubMed Central
Figure 5 Schematic representation of the most important events known to be induced in S. cerevisiae after exposure to high [↑] and low [↓] concentrations of PMKT and PMKT2. Figure adapted and reproduced with permission (Santos et al. 2011; Santos et al. 2013) [42,74].
Figure 5 Schematic representation of the most important events known to be induced in S. cerevisiae after exposure to high [↑] and low [↓] concentrations of PMKT and PMKT2. Figure adapted and reproduced with permission (Santos et al. 2011; Santos et al. 2013) [42,74].CC BY · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 199 references

Research works printed but not linked: 4

  1. Hansen, 1904, Grundlinien zur Systematik der Saccharomyceten, Zentralbl. Bakteriol. Parasitenk. Abt. II, 12, 529
  2. Deak, T., and Beuchat, L. (1996). Handbook of Food Spoilage Yeasts, Crc Series in Contemporary Food Science, CRC Press. [2nd ed.].
  3. Ohta, 1984, Production, purification and characterization of HYI, an antiyeast substance, produced by Hansenula saturnus, Agric. Biol. Chem., 48, 903
  4. Keszthelyi, 2006, Characterisation of anticryptococcal Fc-1 toxin of Filobasidium capsuligenum, Acta Biol. Szeged., 50, 155

Cited by

Sorted by citations

Related

See all

Metadata

Authors
Belda, I., Ruiz, J., Alonso, A., Marquina, D., & Santos, A.
Affiliations
  • Universidad Complutense de Madrid (ES)
  • Department of Microbiology, Biology Faculty, Complutense University of Madrid, 28040 Madrid, Spain
Corresponding author
Santos, Antonio
ORCID
Venue
Toxins
Publisher
MDPI AG
Published
2017-03-23
Volume
9
Issue
4
Pages
112
ISSN
2072-6651 (ISSN-L)
DOI
10.3390/toxins9040112
PMC
PMC5408186
OpenAlex
W2603690755
Cited by
111
References
199
Citations by year
2026: 9 · 2025: 16 · 2024: 15 · 2023: 8 · 2022: 16 · 2021: 14 · 2020: 13 · 2019: 13 · 2018: 1 · 2017: 6
FWCI
0.84
Type
journal article
Language
en
Open access
Licence
Locations
  • Toxins (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Library Open Repository (Universidad Complutense Madrid) (submittedVersion, cc-by)
Funders
  • European Community (AIR CT93-0830)
  • Universidad Complutense-Community of Madrid (PR1/03-11632, CCG07-UCM/AGR-2612, GR45/06, GR69/06, GR74/07, GR58/08, GR35/10-A)
  • CDTI-MINECO-Centre for the Development of Industrial Technology (IDI-20130192, IDI-20140448, IDI-20160102)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Immunology and Microbiology › Microbiology › Yeasts and Rust Fungi Studies
  • Life Sciences › Immunology and Microbiology › Virology › Plant and Fungal Interactions Research
Keywords
Pichia membranifaciens, killer toxin, (1→6)-β-D-glucan, mannoproteins, plasma membrane ion transport, HOG pathway, S phase arrest, apoptosis, biological control agents, Botrytis cinerea, Brettanomyces bruxellensis, wine fermentation, antifungal agents
MeSH terms
Humans, Pichia, Killer Factors, Yeast

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review