Arginine-Enhanced Antimicrobial Activity of Nanozymes against Gram-Negative Bacteria

© 2023 Wiley-VCH GmbH..

The continuous reduction of clinically available antibiotics has made it imperative to exploit more effective antimicrobial therapies, especially for difficult-to-treat Gram-negative pathogens. Herein, it is shown that the combination of an antimicrobial nanozyme with the clinically compatible basic amino acid L-arginine affords a potent treatment for infections with Gram-negative pathogens. In particular, the antimicrobial activity of the antimicrobial nanozyme is dramatically increased by ≈1000-fold after L-arginine stimulation. Specifically, the combination therapy enhances bacterial outer and inner membrane permeability and promotes intracellular reactive oxygen species (ROS) generation. Moreover, the metabolomic and transcriptomic results reveal that combination treatment leads to the increased ROS-mediated damage by inhibiting the tricarboxylic acid cycle and oxidative phosphorylation, thereby inducing an imbalance of the antioxidant and oxidant systems. Importantly, L-arginine dramatically significantly accelerates the healing of infected wounds in mouse models of multidrug-resistant peritonitis-sepsis and skin wound infection. Overall, this work demonstrates a novel synergistic antibacterial strategy by combining the antimicrobial nanozymes with L-arginine, which substantively facilitates the nanozyme-mediated killing of pathogens by promoting ROS production.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:13

Enthalten in:

Advanced healthcare materials - 13(2024), 4 vom: 03. Feb., Seite e2301332

Sprache:

Englisch

Beteiligte Personen:

Zhao, Zihan [VerfasserIn]
Wen, Shu'an [VerfasserIn]
Song, Ningning [VerfasserIn]
Wang, Lixiang [VerfasserIn]
Zhou, Yuan [VerfasserIn]
Deng, Xue [VerfasserIn]
Wu, Changbu [VerfasserIn]
Zhang, Guili [VerfasserIn]
Chen, Jun [VerfasserIn]
Tian, Guo-Bao [VerfasserIn]
Liang, Minmin [VerfasserIn]
Zhong, Lan-Lan [VerfasserIn]

Links:

Volltext

Themen:

94ZLA3W45F
Anti-Bacterial Agents
Anti-Infective Agents
Arginine
Bacterial infections
Gram-negative pathogens
Journal Article
L-arginine
Nanozyme adjuvants
Nanozymes
Reactive Oxygen Species

Anmerkungen:

Date Completed 07.02.2024

Date Revised 07.02.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1002/adhm.202301332

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM364161647