Essential Oil and Phytoconstituent (linalool) from Homalomena Aromatica Schott. Rhizomes Exhibit Antibacterial and Synergistic Effects with Beta-Lactam Antibiotics Against Carbapenem-resistant Enterobacteriaceae (CRE) and Methicillin Resistant S. Aureus (MRSA) Pathogens

Homalomena aromatica Schott. (HA) locally known as "Sugandhmantri" in India is a perennial herb commonly found in Assam, Northeast India and popular for its aromatic and medicinal properties. The main aim of this study was to determine the phytoconstituents of the essential oil (HA-EO) extracted from the rhizomes of Homalomena aromatica, purify its major phytoconstituent (HA-EOC-L) and examine the antibacterial activity. Further the study investigated the synergistic effect of both HA-EO and HA-EOC-L with beta lactam antibiotics against a panel of multi drug resistant (MDR) bacterial pathogens comprising CRE (Carbapenem resistant Enterobacteriaceae namely Escherichia coli & Klebsiella pneumonia genetically harboring NDM/OXA enzymes that deactivates major beta-lactam antibiotics including carbapenem) and MRSA (Methicillin Resistant Staphylococcus aureus harboring mecA gene that encodes PBP2a protein and attributes to antibiotic resistance). Gas chromatography - Mass spectrometry (GC-MS) analyses of HA-EO displayed a total of 177 phytoconstituents with Linalool (mono-terpene alcohol) (38.6 %), terpinen-4-ol (9.5 %), gamma terpinene, and gamma muurolene (3.6 %) as the major class. The major phytoconstituent (Linalool) HA-EOC-L of this lot was purified by fractional distillation. In vitro investigation of the antibacterial activity of HA-EO and HA-EOC-L demonstrated its potential antibacterial activity with MIC 134-1075 mu g/ml and 75-606 mu g/ml against MDR bacteria (CRE & MRSA) respectively. Further, testing the combinatorial activity of HA-EO and HA-EOC-L with beta-lactam antibiotics [(ceftriaxone-CRO (third generation cephalosporin) and meropenem-MEP (carbapenem)], by checkerboard test and time kill assay, demonstrated its synergistic effect towards MDR bacteria with HA-EOC-L showing better adjuvant activity with fractional inhibitory concentration index values (FICI) ranging from 0.13 to 0.49. The results emphasize the significant use of HA-EO and its constituent (HA-EOC-L) as an antibiotic-adjuvant agent to combat MDR infections propounded by the MRSA and CRE indicating HA with its beneficial secondary metabolites as a useful plant that can help human health, animal health besides food and cosmetic industry to combat MDR pathogens.