Post-translational modification of ESKAPE pathogens as a potential target in drug discovery

Area of Science:

• Microbiology
• Molecular Biology
• Biochemistry

Background:

• ESKAPE pathogens are increasingly prevalent and exhibit significant antimicrobial resistance.
• These pathogens employ various post-translational modifications (PTMs) to disrupt host cell functions.
• Understanding these modifications is crucial for combating infections caused by these resistant bacteria.

Purpose of the Study:

• To review and categorize the diverse post-translational modifications (PTMs) utilized by ESKAPE pathogens.
• To elucidate how these bacterial PTMs interact with and alter host cell pathways.
• To highlight the potential of targeting PTMs for novel antibacterial drug development.

Main Methods:

• Literature review and synthesis of existing research on bacterial post-translational modifications.
• Categorization of PTMs based on the type of modification (e.g., chemical group addition, protein conjugation).
• Analysis of reported host-pathogen interactions involving bacterial PTMs.

Main Results:

• ESKAPE pathogens utilize a wide array of PTMs, including acetylation, phosphorylation, methylation, hydroxylation, AMPylation, ADP-ribosylation, glycosylation, isoprenylation, ubiquitylation, UBL conjugation, SUMOylation, eliminylation, and deamidation.
• These PTMs are shown to destabilize or divert critical host cell pathways.
• Specific examples of PTMs and their targeted host proteins are discussed.

Conclusions:

• The extensive repertoire of PTMs in ESKAPE pathogens contributes to their virulence and resistance.
• Detailed knowledge of bacterial PTMs and their host targets offers insights into host-pathogen dynamics.
• Targeting these PTMs presents a promising avenue for the development of novel antibacterial therapies against challenging ESKAPE infections.