Murraya koenigii (L.) Sprengel seeds and pericarps in relation to their chemical profiles: new approach for multidrug resistant Acinetobacter baumannii ventilator-associated pneumonia

Abstract

AbstractAcinetobacterbaumannii is without a doubt one of the most problematic bacteria causing hospital-acquired nosocomial infections in today's healthcare system. To solve the high prevalence of multi-drug resistant (MDR) in A.baumannii, we investigated one of the medicinal plants traditionally used as antibacterial agent; namely Murrayakoenigii (L.) Sprengel. The total methanolic extracts of seeds and pericarps were prepared and their anti-bacterial activity was assessed using the agar diffusion method and minimum inhibitory concentration (MIC) was then calculated as compared to tigecycline. Then, an in-vivo murine model was established which confirmed the promising activity of M.koenigii seeds in demonstrating anti-bacterial and anti-inflammatory actions. The histopathological study of lungs, scoring of pulmonary lesions, counting of bacterial loads after infection by multi-drug resistant A.baumannii all provided evidence to support these findings. LC–MS/MS profiling coupled to molecular networking and chemometrics detected the presence of carbazole alkaloids, and coumarins as dominate metabolites of the active seed extracts. Positively correlated metabolites to antibacterial potential were 6-(2ʹ,3ʹ-dihydroxy-3-methylbutyl)-8-prenylumbelliferone, scopoline, and 5-methoxymurrayatin. An in-silico study was also performed on the crystal structure of MurF from A.baumannii (PDB ID: 4QF5), the studied structures of the mentioned extracts revealed good docking interaction at the active site suggestive of competition with the ATP ligand. These collective findings suggest that extracts of Murrayakoenigii (L.) Sprengel seed is a novel prospective for the discovery of drug candidates against infections caused by MDR A.baumannii.