PMAP-37: A versatile cathelicidin for neutralizing bacteria and viruses

Area of Science:

• Veterinary Medicine
• Immunology
• Microbiology

Background:

• Antimicrobial peptides (AMPs) are crucial for innate immunity, exhibiting direct pathogen-killing and immune-modulating effects.
• Pigs possess eleven cathelicidins, with PMAP-37 being less explored than other variants.
• Understanding PMAP-37's broad-spectrum activity is vital for developing novel veterinary therapeutics.

Purpose of the Study:

• To investigate the antimicrobial and antiviral efficacy of the pig cathelicidin PMAP-37.
• To elucidate the mechanisms underlying PMAP-37's activity against bacteria and its interaction with immune cells.
• To assess PMAP-37's potential as a therapeutic agent in the pig industry.

Main Methods:

• In vitro antimicrobial assays determined minimum bactericidal concentrations (MBCs) against Gram-positive and Gram-negative bacteria.
• Bacterial membrane integrity was assessed using time-kill assays and membrane permeabilization studies.
• Macrophage nitric oxide production, lipopolysaccharide (LPS) binding, and zeta potential were analyzed via flow cytometry and zeta potential measurements.
• Antiviral activity was evaluated against porcine epidemic diarrhea virus (PEDV).

Main Results:

• PMAP-37 demonstrated potent bactericidal activity against Bacillus globigii (2.5 μM) and Escherichia coli (5 μM).
• The peptide rapidly permeabilized E. coli membranes within 5 minutes and neutralized nitric oxide production in macrophages.
• PMAP-37 inhibited LPS binding to macrophages and neutralized negative charges on bacterial membranes and LPS.
• Significant antiviral effects were observed against porcine epidemic diarrhea virus (PEDV).

Conclusions:

• PMAP-37 exhibits broad-spectrum antimicrobial and antiviral properties, targeting key swine pathogens.
• Its mechanisms involve direct membrane disruption and modulation of innate immune responses.
• PMAP-37 presents a promising candidate for therapeutic development in veterinary medicine, particularly for the pig industry.