Identification Of Compounds In Melaleuca AlternifoliaOil With Bacteriostatic Activity In SalmonellaTyphimurium

Abstract

Antibiotic‐resistant infections are projected to cause over 10 million deaths annually by 2050. Despite this growing global crisis, there is waning interest in antimicrobial development due to declining financial incentives and regulatory barriers. There exists a critical need for identification of novel antimicrobial agents. Nearly 75% of US FDA‐approved antibiotics are derived from natural sources. Both plant oils and extracts have been recognized for their potent antimicrobial properties in Gram‐positive and –negative bacteria. However, few investigators have thoroughly explored the effects of individual active compounds that compose these oils. Melaleuca alternifolia (tea tree) oil has been shown to exert broad‐spectrum antimicrobial effects in several bacterial species. We hypothesized that these properties are attributable to monoterpenoid compounds that can diffuse through and disrupt cell membranes. Seven of the most abundant monoterpenoids in Melaleuca alternifolia (tea tree) oil [ρ‐cymene, eucalyptol, (R)‐(+)‐limonene, linalool, terpinen‐4‐ol, α‐terpinene, and terpinolene] were tested individually against SalmonellaTyphimurium, a Gram‐negative bacterium with up to 70% of strains exhibiting resistance to one or more antibiotic. The Mueller‐Hinton agar well diffusion test was used to determine antimicrobial activity through measurement of zones of inhibition. The minimal inhibitory concentration (MIC) and half‐maximal inhibitor concentration (IC50) of the subset of compounds exhibiting antimicrobial effects (linalool, terpinen‐4‐ol, α‐terpinene, and terpinolene) were also determined. MIC and IC50 values were 0.78% ‐ 6.25% and 1.5% ‐ 50% vol/vol, respectively. Each compound exerted its effects through bacteriostatic mechanisms as determined by time‐kill assays. These data highlight a continued role for natural products in the search for novel antimicrobials and importantly, identify the chemical components of Melaleuca alternifolia oil that confer its antimicrobials effects.