A phospholipase B effector exploits membrane lipid divergence to drive inter-Bacteroides competition and enables universal genome editing.
- 1State Key Laboratory of Microbial Technology, Shandong University, Qingdao, China.
Abstract
The Type VI secretion system (T6SS) mediates interbacterial competition, yet the mechanisms underlying its effector diversity and cell-targeting specificity remain poorly understood. Here, we identify Btle, a phospholipase B (PLB) effector defining a unique Tle subfamily (Tle7), encoded in approximately 18.0% of Bacteroides fragilis strains. Lipidomic profiling reveals that Btle preferentially targets Bacteroides glycerophospholipids, disrupting membrane integrity and driving strict inter-Bacteroides competition, with self-intoxication prevented by the cognate immunity protein Btli1. Guided by structural modeling and rational mutagenesis, we developed a Btle variant (BtleM) that evades Btli1 neutralization, establishing a broadly applicable counterselection marker for homologous recombination across Bacteroides. Secretion assays combined with AlphaFold structural prediction demonstrate that Btle delivery depends on a dual-effector complex, uncovering a conserved secretion mechanism within this genus. Collectively, this work expands the Tle superfamily with a calcium-dependent PLB effector, clarifies how glycerophospholipid compositional divergence shapes interbacterial targeting specificity, and establishes a universal counterselection strategy for genetic manipulation of gut Bacteroides.
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BibTeX
@article{xu2026phospholipase,
title = {{A phospholipase B effector exploits membrane lipid divergence to drive inter-Bacteroides competition and enables universal genome editing.}},
author = {Xiaoning Xu and Zhe Chen and Jing He and Yan Yang and Jinghua Xu and Weixun Li and Shuaining Zheng and Xuyao Jiao and Kun Jiang and Shengying Li and Shuang-Jiang Liu and Xiang Gao},
journal = {Gut microbes},
year = {2026},
month = oct,
doi = {10.1080/19490976.2026.2750098},
url = {https://europepmc.org/article/MED/42909602},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - A phospholipase B effector exploits membrane lipid divergence to drive inter-Bacteroides competition and enables universal genome editing.
AU - Xiaoning Xu
AU - Zhe Chen
AU - Jing He
AU - Yan Yang
AU - Jinghua Xu
AU - Weixun Li
AU - Shuaining Zheng
AU - Xuyao Jiao
AU - Kun Jiang
AU - Shengying Li
AU - Shuang-Jiang Liu
AU - Xiang Gao
PY - 2026
DA - 2026/10/23
JO - Gut microbes
DO - 10.1080/19490976.2026.2750098
UR - https://europepmc.org/article/MED/42909602
AB - The Type VI secretion system (T6SS) mediates interbacterial competition, yet the mechanisms underlying its effector diversity and cell-targeting specificity remain poorly understood. Here, we identify Btle, a phospholipase B (PLB) effector defining a unique Tle subfamily (Tle7), encoded in approximately 18.0% of Bacteroides fragilis strains. Lipidomic profiling reveals that Btle preferentially targets Bacteroides glycerophospholipids, disrupting membrane integrity and driving strict inter-Bacteroides competition, with self-intoxication prevented by the cognate immunity protein Btli1. Guided by structural modeling and rational mutagenesis, we developed a Btle variant (BtleM) that evades Btli1 neutralization, establishing a broadly applicable counterselection marker for homologous recombination across Bacteroides. Secretion assays combined with AlphaFold structural prediction demonstrate that Btle delivery depends on a dual-effector complex, uncovering a conserved secretion mechanism within this genus. Collectively, this work expands the Tle superfamily with a calcium-dependent PLB effector, clarifies how glycerophospholipid compositional divergence shapes interbacterial targeting specificity, and establishes a universal counterselection strategy for genetic manipulation of gut Bacteroides.
SN - 1949-0976
SN - 1949-0984
ER -