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TitleA nonenzymatic effector disrupts cell wall homeostasis via OmpA targeting to mediate interbacterial competition.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 122, Issue 41, Page e2513207122, Year 2025
Publish dateOct 14, 2025
AuthorsJing He / Zhe Chen / Kun Jiang / Yan Yang / Weixun Li / Xiaotong Wang / Xiaoning Xu / Shuaining Zheng / Xuyao Jiao / Xudong Chen / Liujie Huo / Bentley Lim / Shuang-Jiang Liu / Xiang Gao /
PubMed AbstractThe human gut microbiome is a dynamic ecosystem where bacteria engage in interspecies competition using molecular weapons such as the type VI secretion system (T6SS). Here, we characterize BteO-BtiO, ...The human gut microbiome is a dynamic ecosystem where bacteria engage in interspecies competition using molecular weapons such as the type VI secretion system (T6SS). Here, we characterize BteO-BtiO, a unique effector-immunity pair in that mediates antagonism via a nonenzymatic mechanism. Microscopy reveals that BteO exposure leads to cell elongation, membrane blebbing, and lysis in sensitive strains. Structural and biochemical analyses demonstrate that BteO disrupts cell wall homeostasis by binding to conserved C-terminal domains of OmpA-family proteins (OmpAs), which are critical for outer membrane integrity. The immunity protein BtiO neutralizes BteO by mimicking the OmpA-binding interface. We further show that bile salts enhance BteO-mediated killing in vitro and that BteO confers a competitive advantage in the mammalian gut. Remarkably, BteO exhibits broad-spectrum activity across species. These findings reveal a nonenzymatic strategy of bacterial antagonism and broaden our understanding of T6SS effector diversity within .
External linksProc Natl Acad Sci U S A / PubMed:41055976 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.9 - 4.18 Å
Structure data

EMDB-64503: Bacteroides fragilis T6SS effector-immunity BteO-BtiO complex
Method: EM (single particle) / Resolution: 4.18 Å

PDB-9uu0:
The structure of Bacteroides fragilis T6SS effector BteO
Method: X-RAY DIFFRACTION / Resolution: 2.72 Å

PDB-9uu1:
Bacteroides fragilis T6SS immunity protein BtiO
Method: X-RAY DIFFRACTION / Resolution: 2 Å

PDB-9uu2:
Outer membrane protein OmpA-c-like domain
Method: X-RAY DIFFRACTION / Resolution: 1.9 Å

Chemicals

ChemComp-HOH:
WATER

ChemComp-IPA:
ISOPROPYL ALCOHOL / alkaloid*YM

Source
  • bacteroides fragilis (bacteria)
  • escherichia coli (strain k12) (bacteria)
  • bacteroides fragilis nctc 9343 (bacteria)
KeywordsTOXIN / Bacteroides fragilis T6SS effector / ANTITOXIN / Bacteroides fragilis T6SS immunity protein / STRUCTURAL PROTEIN / Outer membrane protein OmpA-c-like domain

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