Evaluation of Combinatorial Efficacy of Nisin and Lactoferrin against Pseudomonas Aeruginosa Induced Experimental Pulmonary Infection Model.

Current treatment strategies for Pseudomonas aeruginosa pulmonary infections are limited by severe side effects and the emergence of multidrug resistance. This study evaluated the therapeutic potential of nisin and lactoferrin, two antimicrobial peptides with distinct modes of action, against P. aeruginosa lung infections. In vitro, the combination exhibited potent synergistic antibacterial activity with significant suppression of biofilm formation and pyocyanin production. Morphological analysis by field-emission scanning electron microscopy revealed extensive structural disruption of bacterial cells exposed to the nisin/lactoferrin combination. In a rat model of pulmonary P. aeruginosa infection, co-administration of nisin and lactoferrin prevented weight loss, preserved lung architecture, and achieved 100% survival compared with untreated animals. Treatment significantly reduced bacterial burden in the lungs and trachea, restored cytokine balance, enhanced antioxidant defenses, and lowered oxidative stress. These findings highlight the nisin/lactoferrin combination as a safe and effective peptide-based therapeutic approach for multidrug-resistant P. aeruginosa lung infections.