Converting Bacterial Anti-Stress Metabolites into Bactericidal Agents Using a MOF Nanozyme for Targeted Treatment of Infected Diabetic Ulcers
5 affiliations
- 1East China University of Science and Technology , , 130 Meilong Rd , ,
- 2Changhai Hospital , , ,
- 3University of Bath , , ,
- 4Henan Normal University , , ,
- 5Eastern Hepatobiliary Surgery Hospital , , ,
Abstract
Bacteria evolve sophisticated antistress systems to adapt to lethal conditions such as oxidative stress, and such defensive mechanisms confer them with tolerance against antibacterial therapies. However, whether endogenous antistress metabolites can be repurposed to convert bacterial self-protection into amplified antibacterial mechanisms remains largely unexplored. Here, we designed a galactosyl MOF nanozyme (Gal-MIL/GOx) that upregulates target-specifically the bacterial antistress metabolite, glutathione (GSH), which in turn accelerates cascade catalytic-amplified oxidative damage, facilitating the treatment of infected diabetic ulcers. In a mouse model of Pseudomonas aeruginosa (P. aeruginosa)-infected diabetic wounds, we demonstrated the targeted adhesion of Gal-MIL/GOx to bacteria via selective galactose-LecA interactions, thereby disrupting the integrity of the cell membrane. Notably, this process upregulated bacterial GSH levels and accelerated the cascade catalytic activity of the nanozyme. Significantly, the nanozyme initiated a sustained conversion of local glucose in diabetic wounds to generate high concentrations of H2O2 leading to bacterial membrane rupture. This resulted in a more pronounced leakage of bacterial GSH, which facilitated the conversion of H2O2 into the more toxic •OH, thus amplifying oxidative damage. Through a series of biochemical analyses, we confirmed that the nanozyme can effectively eliminate bacteria, alleviate localized hyperglycemia, and remodel immune homeostasis to promote tissue repair in diabetic mouse wounds. Our findings illustrate a new strategy where MOF nanozymes are used to convert bacterial antistress metabolites into a bactericidal amplifier, thus providing a new avenue for treating infected diabetic ulcers.
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BibTeX
@article{tong2026converting,
title = {{Converting Bacterial Anti-Stress Metabolites into Bactericidal Agents Using a MOF Nanozyme for Targeted Treatment of Infected Diabetic Ulcers}},
author = {Pei-Hong Tong and Wen-Zhen Gu and Jie-Zhi Lin and Hui-Qi Gan and Xi-Le Hu and Tony D. James and Yong-Jun Zheng and Zhao-Fan Xia and Wei-Hong Zhu and He Tian and Xiao-Peng He},
journal = {JACS Au},
year = {2026},
month = nov,
doi = {10.1021/jacsau.6c01494},
url = {https://pubs.acs.org/jaaucr/article/doi/10.1021/jacsau.6c01494/5462947/Converting-Bacterial-Anti-Stress-Metabolites-into},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Converting Bacterial Anti-Stress Metabolites into Bactericidal Agents Using a MOF Nanozyme for Targeted Treatment of Infected Diabetic Ulcers
AU - Pei-Hong Tong
AU - Wen-Zhen Gu
AU - Jie-Zhi Lin
AU - Hui-Qi Gan
AU - Xi-Le Hu
AU - Tony D. James
AU - Yong-Jun Zheng
AU - Zhao-Fan Xia
AU - Wei-Hong Zhu
AU - He Tian
AU - Xiao-Peng He
PY - 2026
DA - 2026/11/03
JO - JACS Au
DO - 10.1021/jacsau.6c01494
UR - https://pubs.acs.org/jaaucr/article/doi/10.1021/jacsau.6c01494/5462947/Converting-Bacterial-Anti-Stress-Metabolites-into
AB - Bacteria evolve sophisticated antistress systems to adapt to lethal conditions such as oxidative stress, and such defensive mechanisms confer them with tolerance against antibacterial therapies. However, whether endogenous antistress metabolites can be repurposed to convert bacterial self-protection into amplified antibacterial mechanisms remains largely unexplored. Here, we designed a galactosyl MOF nanozyme (Gal-MIL/GOx) that upregulates target-specifically the bacterial antistress metabolite, glutathione (GSH), which in turn accelerates cascade catalytic-amplified oxidative damage, facilitating the treatment of infected diabetic ulcers. In a mouse model of Pseudomonas aeruginosa (P. aeruginosa)-infected diabetic wounds, we demonstrated the targeted adhesion of Gal-MIL/GOx to bacteria via selective galactose-LecA interactions, thereby disrupting the integrity of the cell membrane. Notably, this process upregulated bacterial GSH levels and accelerated the cascade catalytic activity of the nanozyme. Significantly, the nanozyme initiated a sustained conversion of local glucose in diabetic wounds to generate high concentrations of H2O2 leading to bacterial membrane rupture. This resulted in a more pronounced leakage of bacterial GSH, which facilitated the conversion of H2O2 into the more toxic •OH, thus amplifying oxidative damage. Through a series of biochemical analyses, we confirmed that the nanozyme can effectively eliminate bacteria, alleviate localized hyperglycemia, and remodel immune homeostasis to promote tissue repair in diabetic mouse wounds. Our findings illustrate a new strategy where MOF nanozymes are used to convert bacterial antistress metabolites into a bactericidal amplifier, thus providing a new avenue for treating infected diabetic ulcers.
SN - 2691-3704
ER -