Thyme, Oregano, and Cinnamon Essential Oils: Investigating Their Molecular Mechanism of Action for the Treatment of Bacteria-Induced Cystitis

Pathogen infections, exacerbated by emerging drug resistance,
remain
among the most challenging health issues, for which multitargeting
approaches may offer effective solutions. In this context, medicinal
plants, including essential oils, provide complex mixtures of diverse
molecules that can exert therapeutic effects, either alone or synergistically
with established antibiotics. Although several databases comprehensively
collect information on the antibacterial properties of medicinal plants,
including chemical composition, bioactivity data, and ethnobotanical
uses, there is a notable lack of tools to hypothesize mechanisms of
action. To address this gap, we developed a computational pipeline
that integrates chemoinformatics and bioinformatics, specifically
designed for scenarios in which only the chemical composition of a
complex mixture of natural phytocompounds is available. Beginning
with an ultralarge, structure-based screening across thousands of
proteins and their potential binding sites of six bacterial species,
we used the predicted targets as input for bioinformatics tools commonly
employed in the omics fields, such as pathway enrichment analysis
and network analysis. Using this pipeline, we modeled how the essential
oils of thyme, oregano, and cinnamon exert antibacterial activity
against six bacterial pathogens. Applied here in the context of urinary
tract infection, but extendable to other therapeutic scenarios, this
pipeline provides a novel protocol for mode of action investigation
and experimental prioritization, to be applied in drug discovery involving
natural substances.