Design and Evaluation of Short Bovine Lactoferrin-Derived Antimicrobial Peptides against Multidrug-Resistant...

Area of Science:

• Microbiology
• Biochemistry
• Drug Discovery

Background:

• Enterococcus faecium is a significant nosocomial pathogen due to increasing antibiotic resistance.
• Antimicrobial peptides (AMPs) offer a potential alternative to conventional antibiotics.

Purpose of the Study:

• To develop novel, short, and chemically simple antimicrobial peptides (AMPs) based on the bovine lactoferrin (LfcinB6) motif.
• To evaluate the efficacy of these AMPs against drug-resistant Enterococcus faecium, including their activity against biofilms and persister cells.

Main Methods:

• Design and synthesis of AMPs with selective amino acid composition, fixed charge, and hydrophobicity.
• Determination of minimal inhibitory concentration (MIC) against E. faecium isolates.
• Assessment of biofilm inhibition and disruption, and elimination of persister cells.
• Analysis of membrane depolarization and alteration of metabolic pathways.
• Evaluation in an ex vivo porcine skin infection model.

Main Results:

• Peptides 5L and 6L exhibited potent antibacterial activity against E. faecium (MIC 4-16 µg/mL).
• Both peptides significantly inhibited biofilm formation and disrupted established biofilms.
• Peptides 5L and 6L effectively eliminated E. faecium persister cells.
• Treatment with 5L and 6L led to membrane depolarization and increased membrane fluidity.
• Peptide 5L altered key metabolic pathways, including the tricarboxylic acid cycle and purine metabolism.
• In an ex vivo model, peptide 5L eradicated both exponential and persister E. faecium cells.

Conclusions:

• The study presents a strategy for developing narrow-spectrum, selective AMPs.
• Peptide 5L demonstrates significant potential as a therapeutic candidate against Enterococcus faecium infections.