Antibacterial Activity of a Cationic Antimicrobial Peptide against Multidrug-Resistant Gram-Negative Clinical...

Area of Science:

• Microbiology
• Biochemistry
• Drug Discovery

Background:

• Antimicrobial resistance (AMR) poses a significant global health threat, diminishing antibiotic efficacy.
• Multidrug-resistant (MDR) Gram-negative bacteria, including Klebsiella pneumoniae (MDRKp) and Pseudomonas aeruginosa (MDRPa), are particularly concerning.
• Cationic antimicrobial peptides (CAMPs) offer a promising alternative therapeutic strategy against MDR strains.

Purpose of the Study:

• To evaluate the antibacterial activity of a cecropin D-like peptide (ΔM2) against clinical isolates of MDRKp and MDRPa.
• To investigate the interaction of ΔM2 with bacterial membrane models and genomic DNA.
• To assess the potential of ΔM2 as a novel antimicrobial agent.

Main Methods:

• In vitro antibacterial activity was determined using broth microdilution assays to establish MIC and MBC values.
• Interactions with lipid membrane models (DMPC/DMPG) were studied using differential scanning calorimetry.
• Peptide-DNA interactions were analyzed via electronic absorption spectroscopy to detect DNA denaturation.

Main Results:

• The peptide ΔM2 exhibited strong bactericidal effects against MDRKp and MDRPa, with MIC/MBC values ranging from 4 to 16 μg/mL.
• ΔM2 significantly altered the thermotropic behavior of dually-lipid bacterial membrane models, indicating membrane disruption.
• Electronic absorption studies revealed a hyperchromic effect upon peptide-DNA interaction, suggesting ΔM2 denatures bacterial DNA.

Conclusions:

• The cecropin D-like peptide ΔM2 demonstrates potent in vitro activity against clinically relevant MDR Gram-negative bacteria.
• ΔM2 exerts its bactericidal effect through mechanisms involving bacterial membrane disruption and DNA denaturation.
• These findings highlight the therapeutic potential of ΔM2 as a novel antimicrobial agent against challenging MDR infections.