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Related Experiment Video

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Author Spotlight: Exploring Cytoskeletal Dynamics to Unveil Novel Antibiotics Through Innovative Cell-Based Assays

Author Spotlight: Exploring Cytoskeletal Dynamics to Unveil Novel Antibiotics Through Innovative Cell-Based Assays

Published on: April 26, 2024

Proteostasis-targeted antibacterial strategies.

Yoon Chae Jeong^1,2, Seong-Hyeon Kim¹, Seongjoon Moon¹

¹Department of Biological Sciences, Ajou University, Suwon 16499, Republic of Korea.

Journal of Microbiology (Seoul, Korea)

|February 25, 2026

Summary

Targeting bacterial protein quality control offers a new way to fight infections. These proteostasis strategies are effective against antibiotic-tolerant bacteria and may help overcome resistance.

Keywords:

APP BacPROTAC chaperone persister protease protein quality control system proteostasis

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Area of Science:

Microbiology
Molecular Biology
Drug Discovery

Background:

Bacterial survival and antibiotic tolerance are linked to protein quality control systems.
Conventional antibiotics face challenges due to bacterial adaptation and resistance.
Targeting molecular chaperones and proteases presents a novel antibacterial strategy.

Purpose of the Study:

To review the mechanistic basis of proteostasis-centered antibacterial strategies.
To summarize recent developments in targeting bacterial protein quality control.
To discuss the translational potential of these novel approaches.

Main Methods:

Review of recent literature on proteostasis and antibacterial strategies.
Analysis of molecular mechanisms involving chaperones and proteases.
Evaluation of novel therapeutic modalities like small molecules, APPs, and BacPROTACs.

Main Results:

Proteostasis-targeted approaches are effective against antibiotic-tolerant persister and VBNC cells.
Strategies include modulating chaperone/protease activity, inducing proteotoxic stress, and using bacterial PROTACs.
Combining proteostasis inhibitors with conventional antibiotics enhances bactericidal efficacy.

Conclusions:

Proteostasis-centered strategies offer a promising avenue to combat bacterial infections and overcome antimicrobial resistance.
These approaches are effective against both actively dividing and dormant bacterial populations.
Further development holds potential for new antibacterial therapies.