DNA replication proteins as potential targets for antimicrobials in drug-resistant bacterial pathogens

Area of Science:

• Microbiology
• Drug Discovery
• Molecular Biology

Background:

• Antimicrobial resistance (AMR) necessitates novel therapeutic strategies.
• DNA replication is a critical cellular process and a promising antimicrobial target.
• Current clinically used antimicrobials targeting DNA replication are limited, primarily to gyrase/topoisomerase inhibitors.

Purpose of the Study:

• To review diverse antimicrobial compounds targeting bacterial DNA replication.
• To highlight challenges in developing novel antimicrobial drugs against DNA replication machinery.
• To underscore the potential of targeting the bacterial replisome for new drug development.

Main Methods:

• Comprehensive literature review of antimicrobial compounds targeting DNA replication.
• Analysis of existing drug classes and their mechanisms of action.
• Identification of essential proteins within the bacterial replisome as potential drug targets.

Main Results:

• A wide array of antimicrobial compounds targeting various aspects of DNA replication exist.
• Gyrase and topoisomerase inhibitors represent the most clinically advanced class.
• Significant opportunities exist for developing inhibitors targeting other essential replisome components.

Conclusions:

• Targeting bacterial DNA replication offers a viable strategy to combat AMR.
• Developing novel antimicrobials against the replisome requires addressing current challenges.
• Further research into diverse DNA replication targets is crucial for future antimicrobial development.