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Animal model, LC/MS/MS, multidrug-resistant Acinetobacter baumannii, Murraya koenigii, Murraya paniculata
Abstract:
Summary Antibiotic resistance is now deemed a worldwide problem that puts public health at risk. The potential of Murraya (Murraya koenigii (L.) Spreng. and Murraya paniculata (L.) Jacq.) leaves and stems as antibacterial agents against multidrug-resistant Acinetobacter baumannii (MDRAB) was assessed in our study. First, screening was performed by disc diffusion assay, and minimum inhibitory concentration values were then determined as compared to tigecycline. A. baumnii mouse model of infection was established to substantiate the antibacterial activity of Murraya species. Results revealed high antimicrobial activity for stem of both plants where leaves showed moderate to weak activity. Phytochemical characterisation revealed the identification of 129 metabolites belonging to different classes of compounds viz. coumarins, carbazole alkaloids, flavonoids, phenolic acids, and miscellaneous. In vivo data from the animal model supported the high efficiency of M. paniculata stems as promising extract for lead candidates against MDRAB pulmonary infections. Inhibition of its essential MurF (UDP-N-acetylmuramoyl-tripeptide-D-alanyl-d-alanine ligase) protein has been reported as a potential target for broad-spectrum drugs. In silico results after molecular docking to MurF from Acinetobacter baumannii (PDB ID: 4QF5) showed competitive binding mode to ATP ligand at the active site predicting antibacterial activity of the tested compounds. Furthermore, chlorogenic acid, caffeic acid, sinapic acid, feruloyl agmatine, and mahanimbidine were detected as the key discriminatory metabolites correlated with antibacterial activity. To our knowledge, this is the first in vivo anti-MDRAB study for the investigated plant. Murraya plants have enormous possibility for the discovery of novel bioactive compounds which could combat against resistant microorganisms.
