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Intein Inhibitors as Novel Antimicrobials: Protein Splicing in Human Pathogens, Screening Methods, and Off-Target
Diana A Wall1, Seanan P Tarrant1, Chunyu Wang2,3
1Department of Chemistry, College of the Holy Cross, Worcester, MA, United States.
Frontiers in Molecular Biosciences
|October 25, 2021
Summary
Inteins, proteins crucial for pathogen survival, are absent in humans. Inhibiting intein activity offers a promising strategy for developing novel antimicrobial therapies against pathogenic microbes.
Area of Science:
- Biochemistry
- Microbiology
- Drug Discovery
Background:
- Protein splicing, mediated by inteins, is essential for pathogen function but absent in metazoans.
- Inteins are highly abundant in microbial pathogens, making them attractive antimicrobial targets.
- Understanding intein mechanisms is key to developing targeted therapies.
Purpose of the Study:
- To review essential intein-containing proteins in pathogenic mycobacteria and fungi.
- To highlight successful strategies for inhibiting intein activity.
- To discuss bioanalytical methods for screening intein inhibitors.
Main Methods:
- Review of literature on inteins in pathogenic mycobacteria and fungi.
- Analysis of studies demonstrating intein inhibition and its effects.
- Examination of bioanalytical techniques for intein activity screening.
Main Results:
- Identified key intein-dependent proteins in pathogenic mycobacteria and fungi.
- Demonstrated proof-of-concept for intein inhibition impacting pathogen fitness.
- Reviewed various bioanalytical methods for screening intein activity.
Conclusions:
- Intein inhibition is a viable strategy for antimicrobial drug development.
- Targeting inteins offers specificity due to their absence in metazoans.
- Further research into intein inhibitors and potential off-target effects is warranted.
