Structural basis of cooperative neutralization of the PldB toxin by immunity proteins in Pseudomonas aeruginosa
- 1Department of Pharmacology, SUSTech Homeostatic Medicine Institute, School of Medicine, Institute for Biological Electron Microscopy, Southern University of Science and Technology, Shenzhen, Guangdong, China
- 2College of Life Sciences, Baoding Key Laboratory of Cancer and Aging, Engineering Research Center of Ecological Safety and Conservation in Beijing-Tianjin-Hebei (Xiong’an New Area) of MOE, Hebei University, Baoding, Hebei, China
Abstract
PldB, a type VI secretion system-dependent phospholipase D (PLD) effector secreted by multidrug-resistant Pseudomonas aeruginosa, alters host cell membrane permeability and facilitates pathogen internalization. Its cytotoxic activity is neutralized by three cognate immunity proteins—PA5086, PA5087, and PA5088—which protect the bacterium from self-intoxication. However, the underlying mechanism remains unclear. Through quantitative and qualitative analyses, we demonstrate that these three immunity proteins function cooperatively to inhibit PldB toxicity. Cryogenic electron microscopy of the PldB−PA5088 complex reveals that PA5088 binds to the HKD2 domain of PldB primarily through electrostatic interactions, markedly reducing the volume of its active center. Interaction studies using domain‑specific truncated PldB variants, together with enzyme activity assays, identify distinct copy numbers and binding regions for PA5086, PA5087, and PA5088 in their association with PldB. Collectively, our findings provide mechanistic insights into immunity protein-mediated neutralization of PldB toxicity, offering a potential foundation for designing PLD-targeting therapeutics against P. aeruginosa infection.
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BibTeX
@article{yang2026structural,
title = {{Structural basis of cooperative neutralization of the PldB toxin by immunity proteins in Pseudomonas aeruginosa}},
author = {Xiaoyun Yang and Jiawen Yang and Hong Wang and Xiuhua Liu and Zongqiang Li},
journal = {Communications Biology},
year = {2026},
month = jul,
doi = {10.1038/s42003-026-10681-3},
url = {https://doi.org/10.1038/s42003-026-10681-3},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Structural basis of cooperative neutralization of the PldB toxin by immunity proteins in Pseudomonas aeruginosa
AU - Xiaoyun Yang
AU - Jiawen Yang
AU - Hong Wang
AU - Xiuhua Liu
AU - Zongqiang Li
PY - 2026
DA - 2026/07/14
JO - Communications Biology
DO - 10.1038/s42003-026-10681-3
UR - https://doi.org/10.1038/s42003-026-10681-3
AB - PldB, a type VI secretion system-dependent phospholipase D (PLD) effector secreted by multidrug-resistant Pseudomonas aeruginosa, alters host cell membrane permeability and facilitates pathogen internalization. Its cytotoxic activity is neutralized by three cognate immunity proteins—PA5086, PA5087, and PA5088—which protect the bacterium from self-intoxication. However, the underlying mechanism remains unclear. Through quantitative and qualitative analyses, we demonstrate that these three immunity proteins function cooperatively to inhibit PldB toxicity. Cryogenic electron microscopy of the PldB−PA5088 complex reveals that PA5088 binds to the HKD2 domain of PldB primarily through electrostatic interactions, markedly reducing the volume of its active center. Interaction studies using domain‑specific truncated PldB variants, together with enzyme activity assays, identify distinct copy numbers and binding regions for PA5086, PA5087, and PA5088 in their association with PldB. Collectively, our findings provide mechanistic insights into immunity protein-mediated neutralization of PldB toxicity, offering a potential foundation for designing PLD-targeting therapeutics against P. aeruginosa infection.
SN - 2399-3642
ER -