Antimicrobial peptide selection from Lippia spp leaf transcriptomes.

Area of Science:

• Biochemistry
• Molecular Biology
• Pharmacology

Background:

• Antimicrobial resistance (AMR) is a global health crisis, necessitating novel antimicrobial agents.
• Plant transcriptomes offer a rich source for identifying novel antimicrobial peptide (AMP) precursors.
• Developing AMPs with potent activity and reduced toxicity is crucial.

Purpose of the Study:

• To identify and synthesize novel antimicrobial peptides from *L. rotundifolia* and *L. alba* leaf transcriptomes.
• To modify and optimize identified AMPs for enhanced antimicrobial efficacy and reduced hemolytic activity.
• To establish a predictive method for developing safe and effective antimicrobial agents from plant mRNA libraries.

Main Methods:

• In silico screening of *L. rotundifolia* and *L. alba* transcriptomes to identify putative antimicrobial peptide (AMP) sequences.
• Chemical synthesis and biological activity testing of selected AMPs against Gram-positive and Gram-negative bacteria.
• Modification and computational modeling of lead AMPs to reduce hemolytic effects and enhance stability.

Main Results:

• 120 putative AMP mRNA sequences were identified, with eight synthesized and tested.
• Synthesized AMPs exhibited broad-spectrum antibacterial activity but also significant hemolytic effects.
• Modified AMP variants demonstrated drastically reduced (down to 0%) hemolytic activity while retaining or improving antimicrobial properties.

Conclusions:

• Plant mRNA libraries are a viable source for discovering and engineering novel antimicrobial peptides.
• Peptide modification strategies can effectively mitigate hemolytic toxicity, leading to safer therapeutic candidates.
• This approach offers a promising pathway for developing next-generation antimicrobials to combat resistance.