Related Experiment Video
Updated: Aug 11, 2026

09:42
Using SecM Arrest Sequence as a Tool to Isolate Ribosome Bound Polypeptides
Published on: June 19, 2012
SsrA-Based Targeted Protein Degradation in Escherichia coli
Qichang Nie1, Terrence Chi-Kong Lau2
1Department of Biomedical Sciences, College of Biomedicine, City University of Hong Kong, Kowloon, Hong Kong, SAR, China.
Methods in Molecular Biology (Clifton, N.J.)
|August 10, 2026
Summary
Bacterial PROTACs offer a novel approach to combat antimicrobial resistance by targeting drug-resistant proteins like CTX-M-14. This method resensitizes bacteria to antibiotics, reviving their efficacy.
Area of Science:
- Drug discovery and development
- Molecular biology
- Antimicrobial resistance research
Background:
- Targeted protein degradation is a promising drug discovery strategy.
- Proteolysis-targeting chimeras (PROTACs) harness the proteasome to degrade proteins.
- Antimicrobial resistance (AMR) is a growing global health threat, driven by drug-resistant bacteria.
Purpose of the Study:
- To develop a novel bacterial PROTAC (BacPROTAC) system.
- To target and degrade the drug-resistant CTX-M-14 β-lactamase.
- To resensitize AMR bacteria to antibiotics.
Main Methods:
- Utilized an ssrA-based system to create bacterial PROTACs.
- Applied BacPROTACs to target CTX-M-14 in AMR bacteria.
- Assessed the resensitization of bacteria to antibiotics.
Main Results:
- Successfully developed and applied ssrA-based BacPROTACs.
- Demonstrated the degradation of CTX-M-14, a key AMR determinant.
- Showed potential for resensitizing drug-resistant bacteria.
Conclusions:
- Bacterial PROTACs represent a viable strategy for combating AMR.
- This approach can revive the effectiveness of existing antibiotics.
- Opens new therapeutic avenues for treating infections caused by AMR bacteria.
Related Concept Videos
Directing Proteins to the Rough Endoplasmic Reticulum
The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
The Proteasome
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
The Proteasome
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
Stringent Response in E. coli
Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
Regulated Protein Degradation
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
The Unfolded Protein Response
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...

