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Cited by 13Microbial Natural Products and BiosynthesisAntimicrobial Peptides and ActivitiesBacterial Genetics and Biotechnology

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Cyclo(Pro-Tyr) elicits conserved cellular damage in fungi by targeting the [H+]ATPase Pma1 in plasma membrane domains

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Vela-Corcia, D., Hierrezuelo, J., Pérez-Lorente, A. I., Stincone, P., Pakkir Shah, A. K., Grélard, A., Zi-Long, Y., de Vicente, A., Pérez García, A., Bai, L., Loquet, A., Petras, D., Romero, D.·2024·Communications Biology
DOI 10.1038/s42003-024-06947-3PMC PMC11449911

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Abstract

Bioactive metabolites play a crucial role in shaping interactions among diverse organisms. In this study, we identified cyclo(Pro-Tyr), a metabolite produced by Bacillus velezensis, as a potent inhibitor of Botrytis cinerea and Caenorhabditis elegans, two potential cohabitant eukaryotic organisms. Based on our investigation, cyclo(Pro-Tyr) disrupts plasma membrane polarization, induces oxidative stress and increases membrane fluidity, which compromises fungal membrane integrity. These cytological and physiological changes induced by cyclo(Pro-Tyr) may be triggered by the destabilization of membrane microdomains containing the [H+]ATPase Pma1. In response to cyclo(Pro-Tyr) stress, fungal cells activate a transcriptomic and metabolomic response, which primarily involves lipid metabolism and Reactive Oxygen Species (ROS) detoxification, to mitigate membrane damage. This similar response occurs in the nematode C. elegans, indicating that cyclo(Pro-Tyr) targets eukaryotic cellular membranes. Cyclo(Pro-Tyr), a metabolite from Bacillus velezensis, inhibits Botrytis cinerea and Caenorhabditis elegans by disrupting membrane polarization, inducing oxidative stress, and increasing membrane fluidity. These effects trigger lipid metabolism and ROS detoxification, targeting eukaryotic membranes.

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Metadata

Authors
Vela-Corcia, D., Hierrezuelo, J., Pérez-Lorente, A. I., Stincone, P., Pakkir Shah, A. K., Grélard, A., Zi-Long, Y., de Vicente, A., Pérez García, A., Bai, L., Loquet, A., Petras, D., & Romero, D.
Affiliations
  • Consejo Superior de Investigaciones Científicas (ES)
  • University of Tübingen (DE)
  • Centre National de la Recherche Scientifique (FR)
  • Peking University (CN)
  • University of California, Riverside (US)
Corresponding author
Romero, D.
ORCID
Venue
Communications Biology
Publisher
Springer Science and Business Media LLC
Published
2024-10-03
Volume
7
Issue
1
Pages
1253-1253
ISSN
2399-3642 (ISSN-L)
DOI
10.1038/s42003-024-06947-3
PMC
PMC11449911
OpenAlex
W4403101637
Cited by
13
References
4
Citations by year
2026: 9 · 2025: 4
FWCI
3.69
Type
journal article
Language
en
Open access
Licence
Locations
  • Communications Biology (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Universidad de Málaga
  • European Commission (101108450)
  • Deutsche Forschungsgemeinschaft (EXC 2124, TRR261)
  • National Natural Science Foundation of China (32171212)
  • Ministerio de Economía y Competitividad (PID2019-107724GB-I00)
  • Junta de Andalucía
  • Smithsonian Conservation Biology Institute
  • HORIZON EUROPE Framework Programme
  • H2020 European Research Council (637971)
Topics
  • Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Microbial Natural Products and Biosynthesis
  • Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
Bacillus velezensis, Botrytis cinerea, Caenorhabditis elegans, Pma1, H+-ATPase, cell membrane damage, lipid rafts, oxidative stress, membrane fluidity, lipid metabolism, reactive oxygen species scavenging, nematode-fungus interaction, transcriptomic response
MeSH terms
Animals, Antifungal Agents, Cell Membrane, Proton-Translocating ATPases, Caenorhabditis elegans, Reactive Oxygen Species, Oxidative Stress, Botrytis, Membrane Microdomains

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