# Engineering a Gram-Negative Bactericidal Hydrogel: CuxTe Nanozyme Functions as a Specific Killer by Hijacking LPS and Flagella Biosynthesis

## TL;DR

A new hydrogel using copper telluride nanozymes selectively kills gram-negative bacteria by targeting their defense structures and causing oxidative stress.

## Contribution

A gram-negative-specific hydrogel that hijacks LPS and flagella biosynthesis through CuxTe nanozyme activity.

## Key findings

- CuxTe@CG hydrogel induces lethal oxidative stress in gram-negative bacteria by generating ROS and depleting glutathione.
- Transcriptome analysis shows down-regulation of LPS and flagella biosynthesis genes in Pseudomonas aeruginosa.
- The hydrogel effectively eliminates gram-negative pathogens and accelerates wound healing in a P. aeruginosa-infected burn model.

## Abstract

The treatment of gram-negative bacterial infections remains a formidable challenge due to their resilient outer membrane and adaptive evasion mechanisms. Herein, we present a multifunctional nanozyme hydrogel, copper telluride@cationic guar gum (CuxTe@CG), which acts as a gram-negative-specific bactericidal platform. This hydrogel integrates the unique enzymatic and physical properties of urchin-like CuxTe nanozymes with the biocompatible and adhesive cationic guar gum (CG) matrix. The CuxTe@CG hydrogel exhibits synergistic oxidase- and glutathione peroxidase-like activities, catalyzing the generation of reactive oxygen species (ROS) while depleting bacterial glutathione, thereby inducing lethal oxidative stress. Crucially, transcriptome sequencing revealed that the platform specifically targets Pseudomonas aeruginosa by down-regulating key genes involved in lipopolysaccharide (LPS) biosynthesis and flagellar assembly, compromising their primary defense and motility structures. This targeted interference with LPS and flagella amplifies the ROS-mediated attack, leading to enhanced and specific killing of gram-negative pathogens (Escherichia coli, P. aeruginosa, and Klebsiella pneumoniae), effective biofilm disruption, and inhibition. In a P. aeruginosa-infected burn wound model, the CuxTe@CG hydrogel markedly accelerated healing by eliminating bacteria, promoting angiogenesis, and modulating inflammation, all while demonstrating excellent biosafety. This work establishes the CuxTe@CG hydrogel as a robust and targeted therapeutic strategy for combating stubborn gram-negative infections.