Terpineol enhances antibiotic effectiveness and reduces resistance in clinically relevant bacteria
Year: 2025
Type: article
Abstract: The synergistic interaction between natural compounds and existing antibiotics (ABXs) offers a promising strategy to enhance ABX efficacy while mitigating resistance. This study evaluated the potential of terpineol (TER), a monocyclic monoterpene of plant origin with antimicrobial properties, as an enhancer of antibiotic activity against 14 clinically and veterinary relevant bacterial strains, including ESKAPE pathogens identified by WHO as urgent targets. The antimicrobial activity of TER and its synergistic effects with 13 commonly used antibiotics were assessed using the checkerboard microdilution method and isobologram representation, with growth kinetics and time-kill curves generated over 24 h. TER showed antimicrobial activity against 14 tested bacteria. The lowest MIC was 0.25 mg/mL for Acinetobacter baumannii (WHO priority 1). TER was effective (MIC = 0.5 mg/mL) against various Gram-negative and positive bacteria, exhibiting bactericidal activity in all cases. TER formed additive and synergistic relationships with 11 antibiotics. Six combinations demonstrated synergy (FICi≤0.5), 24 showed additivity (0.5<FICi≤1), and 13 exhibited indifference (1<FICi<4), with no antagonism (FICi≥4). The six TER/ABX synergies resulted in 100 % inhibition of bacterial growth, reducing MICs by up to 87.5 %. For the first time, this study demonstrated that TER minimally generates microbial resistance compared to commercial antibiotics. Additionally, TER acted as an Antimicrobial Resistance Modifying Agent, reducing resistance to four ABXs (gentamycin, florfenicol, chloramphenicol, tetracycline) in both Gram-positive and negative bacteria. Given its safety profile endorsed by EPA and FDA, TER emerges as a promising candidate for natural antibiotic enhancement, preventing the development of resistance. • Terpineol exhibits bactericidal activity against 14 pathogenic bacteria. • Terpineol has the lowest MIC for Acinetobacter baumannii (WHO priority 1). • Terpineol formed additive and synergistic relationships with 11 common antibiotics. • The six terpineol/antibiotic synergies achieved 100 % bacterial growth inhibition. • The synergies enhanced antimicrobial activity of commercial antibiotics up to 87.5 %.
Source: Heliyon
Authors: Antonio Valenzuela, Cristina Gan, Natalia Ferrando, Elisa Langa, Diego Ballestero, María Rosa Pino-Otín
Institution: Universidad San Jorge
Language: English
Subfield: Food Science
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,270
Funders: Universidad San Jorge, Gobierno de Aragón
Award: G4308969740
OpenAlex ID: W4414754967
