Systematic discovery of antibacterial and antifungal bacterial toxins.
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
22 Oct 2024
22 Oct 2024
Historique:
received:
18
06
2023
accepted:
30
08
2024
medline:
23
10
2024
pubmed:
23
10
2024
entrez:
22
10
2024
Statut:
aheadofprint
Résumé
Microorganisms use toxins to kill competing microorganisms or eukaryotic cells. Polymorphic toxins are proteins that encode carboxy-terminal toxin domains. Here we developed a computational approach to identify previously undiscovered, conserved toxin domains of polymorphic toxins within 105,438 microbial genomes. We validated nine short toxins, showing that they cause cell death upon heterologous expression in either Escherichia coli or Saccharomyces cerevisiae. Five cognate immunity genes that neutralize the toxins were also discovered. The toxins are encoded by 2.2% of sequenced bacteria. A subset of the toxins exhibited potent antifungal activity against various pathogenic fungi but not against two invertebrate model organisms or macrophages. Experimental validation suggested that these toxins probably target the cell membrane or DNA or inhibit cell division. Further characterization and structural analysis of two toxin-immunity protein complexes confirmed DNase activity. These findings expand our knowledge of microbial toxins involved in inter-microbial competition that may have the potential for clinical and biotechnological applications.
Identifiants
pubmed: 39438720
doi: 10.1038/s41564-024-01820-9
pii: 10.1038/s41564-024-01820-9
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Israel Science Foundation (ISF)
ID : 1535/20
Organisme : Israel Science Foundation (ISF)
ID : 3300/20
Organisme : Israel Science Foundation (ISF)
ID : 1760/20
Organisme : Israel Science Foundation (ISF)
ID : 1600/21
Organisme : Israel Science Foundation (ISF)
ID : 1818/21
Organisme : EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
ID : Adv. Grant # 743016
Organisme : United States - Israel Binational Agricultural Research and Development Fund (BARD)
ID : IS-5492-22 R
Organisme : United States - Israel Binational Agricultural Research and Development Fund (BARD)
ID : IS-5492-22 R
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature Limited.
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