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TitleA conserved adaptor orchestrates co-secretion of synergistic type VI effectors in gut Bacteroidota.
Journal, issue, pagesCell Host Microbe, Vol. 33, Issue 11, Page 1901-1915.e10, Year 2025
Publish dateNov 12, 2025
AuthorsWeixun Li / Shuaining Zheng / Xiaoning Xu / Jing He / Xuyao Jiao / Mingyu Wang / Wei Hu / Shengying Li / Xianzhi Jiang / Bentley Lim / Feng Shao / Xiang Gao /
PubMed AbstractInterbacterial competition is crucial for shaping microbial communities and is often mediated by type VI secretion systems (T6SSs) that inject effectors into competing bacteria. T6SS effectors are ...Interbacterial competition is crucial for shaping microbial communities and is often mediated by type VI secretion systems (T6SSs) that inject effectors into competing bacteria. T6SS effectors are released via structural proteins such as VgrG, but the secretion timing and coordination are unclear. Here, we report two effectors, BtpeA (Bacteroides T6SS phosphatase effector A) and BtaeB (Bacteroides T6SS amidase effector B), within the Bacteroidota T6SS that exert distinct cell-wall destructive activities critical for interspecies competition but whose secretion is interdependent. BtpeA and BtaeB co-secretion requires an adaptor protein, BtapC (Bacteroides T6SS adaptor protein C), that mediates the sequential assembly of the pre-firing complex, VgrG-BtpeA-BtaeB-BtapC. Structural analyses of this quaternary complex elucidate multi-cargo loading mechanisms with a conserved loop in BtaeB serving as a "checkpoint" to ensure BtpeA co-secretion. During mouse colonization, the combined activities of BtpeA and BtaeB significantly exceed the sum of the individual effectors. These findings unveil a T6SS-mediated co-delivery mechanism that ensures functional synergism of effectors, highlighting potential applications in modulating gut microbiota.
External linksCell Host Microbe / PubMed:41072405
MethodsEM (single particle) / X-ray diffraction
Resolution2.11 - 3.06 Å
Structure data

61458

9jg8

EMDB-61458, PDB-9jg8:
Structure of cargo complex (BtpeA-BtaeB-BtapC) bound to the VgrG spike from the Type VI secretion system
Method: EM (single particle) / Resolution: 3.06 Å

PDB-9jdh:
Crystal structure of the T6SS effector BtaeB-NTD from Bacteroides fragilis
Method: X-RAY DIFFRACTION / Resolution: 2.18 Å

PDB-9jdi:
Crystal structure of the type VI secretion system effector-immunity complex BtpeA CTD-BtpiA from Bacteroides fragilis.
Method: X-RAY DIFFRACTION / Resolution: 2.11 Å

Chemicals

ChemComp-PEG:
DI(HYDROXYETHYL)ETHER

ChemComp-HOH:
WATER

ChemComp-GOL:
GLYCEROL

ChemComp-ZN:
Unknown entry

Source
  • bacteroides fragilis (bacteria)
KeywordsANTIMICROBIAL PROTEIN / Bacteroides fragilis / T6SS / effector / Interbacterial antagonism / Immunity / Phosphatase / Co-delivery / effector complex / VgrG spike

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