Cathelicidin Peptide Targets Bacterial Respiration in Drug-Resistant Superbug

Acinetobacter baumannii is a formidable multidrug-resistant (MDR) pathogen responsible for severe hospital-acquired infections, including pneumonia, bloodstream infections, and wound infections, often with high mortality rates. The increasing prevalence of strains resistant to nearly all available antibiotics, including carbapenems, poses a critical global health threat, leading to a desperate need for novel antimicrobial strategies. This study investigates the specific mechanism by which the cathelicidin peptide hc-cath exerts its antibacterial effects against A. baumannii, focusing on its impact on bacterial respiration.

The study revealed that hc-cath significantly inhibited the growth of A. baumannii in a dose-dependent manner. At a concentration of 1 µM, hc-cath reduced bacterial viability by a remarkable 95% within 6 hours compared to untreated controls (p<0.001). This potent bactericidal effect was linked to a drastic disruption of bacterial energy metabolism; treated bacteria showed a 70% decrease in intracellular ATP levels and an 85% reduction in oxygen consumption rates (p<0.001). > The most critical finding was the direct interaction of hc-cath with terminal oxidase bo3, a key enzyme in the bacterial electron transport chain, leading to a 2.3-fold increase in reactive oxygen species (ROS) and severe oxidative stress within the bacteria. In the murine sepsis model, a single 5 mg/kg dose of hc-cath improved survival rates from a mere 10% in the control group to 80% (p<0.01) and reduced bacterial load in the spleen and liver by over 99%.