A nonenzymatic effector disrupts <i>Bacteroides</i> cell wall homeostasis via OmpA targeting to mediate interbacterial competition
Abstract
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 Bacteroides fragilis 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 Bacteroides species. These findings reveal a nonenzymatic strategy of bacterial antagonism and broaden our understanding of T6SS effector diversity within Bacteroides .
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (14)
Jing He
Zhe Chen
Gladstone Institutes, San Francisco, CA, USA.
Kun Jiang
Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, State Key Laboratory of Porous Materials for Separation and Conversion, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), Department of Chemistry
Yan Yang
Weixun Li
State Key Laboratory of Microbial Technology, Shandong University
Xiaotong Wang
Department of Chemistry and Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, 220 Handan Road, Shanghai 200433, P. R. China
Xiaoning Xu
State Key Laboratory of Microbial Technology, Shandong University
Shuaining Zheng
State Key Laboratory of Microbial Technology, Shandong University
Xuyao Jiao
State Key Laboratory of Microbial Technology, Shandong University
Xudong Chen
Ministry of Education Key Laboratory of Protein Science, Tsinghua-Peking Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University
Liujie Huo
State Key Laboratory of Microbial Technology, Shandong University
Bentley Lim
Department of Microbial Pathogenesis and Microbial Sciences Institute, Yale University School of Medicine
Shuang-Jiang Liu
State Key Laboratory of Microbial Technology, Shandong University
Xiang Gao