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TitleFunctional synergy of heteropentameric B subunits underlies virulence in a Salmonella A2B5 toxin.
Journal, issue, pagesPLoS Pathog, Vol. 21, Issue 11, Page e1013684, Year 2025
Publish dateNov 12, 2025
AuthorsDongdong Wang / Zhe Chen / Chunyu Xu / Xuyao Jiao / Min Yue / Xiang Gao /
PubMed AbstractAB5-type toxins are critical virulence factors in bacterial pathogenesis. Despite the identification of various B subunits in AB5 toxins across different pathogens, their assembly mechanisms and ...AB5-type toxins are critical virulence factors in bacterial pathogenesis. Despite the identification of various B subunits in AB5 toxins across different pathogens, their assembly mechanisms and biological significance remain poorly understood. In this study, we identified and characterized a typhoid toxin-like A2B5 toxin, designated diarizonae toxin (DiaT), as a key virulence factor in Salmonella diarizonae. The DiaT genomic islet encodes two distinct B subunits, PltBd1 and PltBd2, which exhibit unique functional roles. Through genetic and functional analyses, we demonstrate that the heteropentameric assembly of PltBd1 and PltBd2 is essential for cytotoxicity, with our data suggesting PltBd1 facilitates toxin secretion and PltBd2 mediates host cell targeting. Cryo-EM structural analysis of endogenously expressed DiaT reveals a heteropentameric holotoxin with a 3:2 stoichiometry of PltBd1 to PltBd2, potentially stabilized by the PltA subunit. These findings uncover a novel assembly mechanism and synergistic functionality between distinct B subunits, advancing our understanding of the evolutionary diversity and functional complexity of AB5 toxins. This work provides new insights into bacterial pathogenesis and highlights potential targets for therapeutic intervention.
External linksPLoS Pathog / PubMed:41223210 / PubMed Central
MethodsEM (single particle)
Resolution2.32 - 3.05 Å
Structure data

62643

9kyb

EMDB-62643, PDB-9kyb:
PltBd1/PltBd2 heteropentameric holotoxin from S. diarizonae
Method: EM (single particle) / Resolution: 2.32 Å

62644

9kyc

EMDB-62644, PDB-9kyc:
PltBd1/PltBd2 heteropentameric holotoxin from E. coli
Method: EM (single particle) / Resolution: 2.94 Å

62645

9kyd

EMDB-62645, PDB-9kyd:
PltBd1 homopentameric holotoxin from E. coli
Method: EM (single particle) / Resolution: 3.05 Å

62646

9kye

EMDB-62646, PDB-9kye:
PltBd2 homopentameric holotoxin from E. coli
Method: EM (single particle) / Resolution: 2.61 Å

Chemicals

ChemComp-HOH:
WATER

Source
  • salmonella enterica subsp. diarizonae (bacteria)
KeywordsTOXIN / heteropentamer / virulence factor

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