Engineered Cationic Antimicrobial Peptides (eCAPs) to Combat Multidrug-Resistant Bacteria.

Area of Science:

• Biochemistry
• Microbiology
• Drug Discovery

Background:

• Antibiotic resistance is a growing global health threat.
• Antimicrobial peptides (AMPs) show potential for selective bacterial killing, bypassing traditional resistance mechanisms.
• Clinical development of AMPs faces hurdles such as reduced activity in serum and lack of in vivo efficacy.

Purpose of the Study:

• To review advancements in engineering helical antimicrobial peptides (AMPs) over the past two decades.
• To highlight strategies addressing challenges in AMP clinical development.
• To showcase promising data for AMPs moving towards clinical application.

Main Methods:

• Engineering of cationic antimicrobial peptides (AMPs) *de novo*.
• Optimization of AMPs under conditions that typically inhibit natural AMP activity.
• Focus on achieving systemic efficacy and overcoming serum-related inhibition.

Main Results:

• Successful engineering of AMPs to maintain activity under inhibitory conditions.
• Demonstration of *de novo* designed AMPs with enhanced properties for overcoming clinical development challenges.
• Identification of promising helical AMP candidates for further investigation.

Conclusions:

• Engineered helical AMPs represent a viable strategy to combat antibiotic resistance.
• Overcoming *in vitro* and *in vivo* challenges is crucial for AMP clinical translation.
• The last two decades have seen significant progress in developing AMPs for therapeutic use.