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. 2022 Oct 13:13:953982.
doi: 10.3389/fphar.2022.953982. eCollection 2022.

Terpenes as bacterial efflux pump inhibitors: A systematic review

Kaio Jefté Santos De Oliveira Dias  1 , Gustavo Marinho Miranda  1 , Jonatas Reis Bessa  2 , Ana Carolina Justino De Araújo  3 , Priscilla Ramos Freitas  3 , Ray Silva De Almeida  3 , Cícera Laura Roque Paulo  3 , José Bezerra De Araújo Neto  3 , Henrique D M Coutinho  3 , Jaime Ribeiro-Filho  1   4
Affiliations

Terpenes as bacterial efflux pump inhibitors: A systematic review

Kaio Jefté Santos De Oliveira Dias et al. Front Pharmacol. .

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.

Keywords: antibiotic resistance; efflux pumps; natural products; systematic review; terpenes.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Description of the search and selection of the studies.
FIGURE 2
FIGURE 2
Pie chart plots of frequency analysis. (A) Strains; (B) terpenes; and (C) efflux pumps. These data were analyzed using the Jeffrey Amazing Statistic Program—JASP Team (2022).
FIGURE 3
FIGURE 3
Chemical structures of the most frequently reported terpenes.
FIGURE 4
FIGURE 4
Illustration of the inhibition of bacterial efflux pumps by terpenes and its impact on antibiotic resistance.
See this image and copyright information in PMC

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