Terpenes as bacterial efflux pump inhibitors: A systematic review

Abstract

Managing antibiotic resistance is a significant challenge in modern pharmacotherapy. While molecular analyses have identified efflux pump expression as an essential mechanism underlying multidrug resistance, the targeted drug development has occurred slower. Thus, considering the verification that terpenes can enhance the activity of antibiotics against resistant bacteria, the present study gathered evidence pointing to these natural compounds as bacterial efflux pump inhibitors. A systematic search for manuscripts published between January 2007 and January 2022 was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol and the following search terms: “Terpene”; AND “Efflux pump”; and “Bacteria.” From a total of 101 articles found in the initial search, 41 were included in this review. Seventy-five different terpenes, 63 bacterial strains, and 22 different efflux pumps were reported, with carvacrol, Staphylococcus aureus SA-1199B, and NorA appearing most frequently mentioned terpene, bacterial strain, and efflux pump (EP), respectively. The Chi-Squared analysis indicated that terpenes are significantly effective EP inhibitors in Gram-positive and Gram-negative strains, with the inhibitory frequency significantly higher in Gram-positive strains. The results of the present review suggest that terpenes are significant efflux pump inhibitors and, as such, can be used in drug development targeting the combat of antibacterial resistance.

Mediterranean Plants with Antimicrobial Activity against Staphylococcus aureus, a Meta-Analysis for Green Veterinary Pharmacology Applications

“…One of the notable properties of terpenes is their antibacterial activity. While the specific mechanisms of action may vary depending on the terpene and the bacterial species, some common mechanisms include disruption of cell membranes, inhibition of enzyme activity, and interference with bacterial growth and replication [ 148 , 149 , 150 , 151 ]. Recently, terpenes have been found to be effective inhibitors of efflux pumps in a diverse range of bacterial strains, suggesting their potential utility in drug development for addressing antibiotic resistance [ 149 ].…”

Essential Oil Compounds in Combination with Conventional Antibiotics for Dermatology

“…There are limited studies investigating interactions between EOCs and conventional antibiotics against Gram-negative bacteria and fungi. Much of the focus has shifted to investigating how EOCs can attenuate virulence factors and resistance mechanisms [ 23 , 25 , 26 ]. Based on current therapies, many existing antibiotic strategies rely on combinations of an antibiotic with an adjuvant to target a resistance mechanism and “resensitize” the micro-organism to the antibiotic [ 16 ].…”

“…These essential oil compounds (EOCs) are responsible for the pharmacological properties of an EO and, more specifically, their antimicrobial properties [ 24 ]. EOCs have been studied independently and are actively being sought as novel chemical entities for antimicrobial development [ 25 , 26 ].…”

Eucalyptus globulus Leaf Aqueous Extract Differentially Inhibits the Growth of Three Bacterial Tomato Pathogens

“…to control the growth of crop-related disease causal agents (reviewed by Raveau, et al [31]). Accordingly, the leaves of E. globulus are characteristically rich in terpenes, flavonoids, and phenolic acids, whose antibacterial activities have already been described [28,32,33], and for that reason, eucalyptus leaf extracts can constitute a great antimicrobial strategy. As a matter of fact, a previous study has reported strong inhibitory properties of E. globulus extracts against human-pathogen bacteria, such as P. aeruginosa [24].…”