In vitro and In vivo Antimicrobial Potential of Lithium Complex against Multi Drug Resistant Acinetobacter baumannii

Acinetobacter baumannii is a Gram-negative ESKAPE pathogen, accountable for lethal nosocomial infections, owing to its high pathogenicity and multi-drug resistance (MDR). Hence, the World Health Organization (WHO) has prioritized this bacterium against which new pharmacophores are required urgently. Therefore, this study evaluates the antimicrobial potential of lithium complex based on salicylic acid, and 1,10-phenanthroline ([Li(phen)2sal]) against MDR A. baumannii (MDRAB) through growth inhibition, time-kill assay, biofilm inhibition, and eradication alongside microscopy. The mechanism of action was proposed by flow cytometry and proteomic analysis. Moreover, its in-vivo efficacy was assessed using A. baumannii-induced pneumonia model in mice. Results showed that lithium complex significantly inhibited the bacterial growth at 16-32 µg/ml. Time kill analysis revealed that the compound retarded the bacterial growth after 2-3 h of treatment. Lithium complex significantly inhibited and eradicated >70% of biofilms at the MIC level which is a key problem of indwelling and prosthetic devices. Light and atomic force microscopy further indicated disarticulated biofilm and ruptured cellular membrane post-lithium complex treatment. Proteomic analysis revealed that lithium complex exerted oxidative stress on A. baumannii which may contribute to cell rupturing. Flow cytometry confirmed the role of lithium complex in cytoplasmic membrane disintegration. The compound ameliorated the pneumonia symptoms at non-toxic doses of 20 and 40 mg/kg in the pre-clinical A. baumannii-induced pneumonia model as evident by the significant reduction in bacterial burden and parenchymal inflammation. Taken together, these findings suggest that the lithium complex can be a potential drug candidate against MDR A. baumannii.