Confined Mechanical Microenvironment Regulated Antibiotic Resistance in 3D Biofilm Aggregates Probed by Scanning Electrochemical Microscopy DOI

Yan Zhou,

Xuan Zhou, Junjie Zhang

et al.

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Antibiotic resistance is a significant global concern. Clinical trials have highlighted discrepancies in antibiotic doses between vivo three-dimensional (3D) biofilms and vitro two-dimensional biofilm models. A critical factor often overlooked the confined mechanical microenvironment (e.g., host extracellular matrix (ECM) stiffness) surrounding biofilms, leading to inaccurate diagnosis increased resistance. Herein, we designed 3D agarose-gel-based model applied scanning electrochemical microscopy (SECM) monitor metabolic dynamics situ, including cellular respiration reactive oxygen species of an embedded single aggregate. We discovered distinct patterns for aggregates stiff soft gels at aggregate level, which was corroborated by transcriptional analysis. Our findings indicate that cues mediate tolerance reducing activity increasing production polymeric substances (EPS). Additionally, identified metabolite glycine enhances tricarboxylic acid cycle, suggesting its potential as adjuvant improve efficacy. Knocking out upregulated EPS-related gene (ΔyjbE) results significantly reduced survival rates ΔyjbE mutants agarose compared wild type, thereby enhancing Overall, our study demonstrates versatility SECM-based strategy investigating both uncovers role ECM stiffness mediating paving way improved clinical strategies treatment.

Language: Английский

Confined Mechanical Microenvironment Regulated Antibiotic Resistance in 3D Biofilm Aggregates Probed by Scanning Electrochemical Microscopy DOI

Yan Zhou,

Xuan Zhou, Junjie Zhang

et al.

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Antibiotic resistance is a significant global concern. Clinical trials have highlighted discrepancies in antibiotic doses between vivo three-dimensional (3D) biofilms and vitro two-dimensional biofilm models. A critical factor often overlooked the confined mechanical microenvironment (e.g., host extracellular matrix (ECM) stiffness) surrounding biofilms, leading to inaccurate diagnosis increased resistance. Herein, we designed 3D agarose-gel-based model applied scanning electrochemical microscopy (SECM) monitor metabolic dynamics situ, including cellular respiration reactive oxygen species of an embedded single aggregate. We discovered distinct patterns for aggregates stiff soft gels at aggregate level, which was corroborated by transcriptional analysis. Our findings indicate that cues mediate tolerance reducing activity increasing production polymeric substances (EPS). Additionally, identified metabolite glycine enhances tricarboxylic acid cycle, suggesting its potential as adjuvant improve efficacy. Knocking out upregulated EPS-related gene (ΔyjbE) results significantly reduced survival rates ΔyjbE mutants agarose compared wild type, thereby enhancing Overall, our study demonstrates versatility SECM-based strategy investigating both uncovers role ECM stiffness mediating paving way improved clinical strategies treatment.

Language: Английский

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