Evidence map›Paper›PMID 40478408›Full record

ArticleNatural products and bioprospecting2025

Mechanisms of action and resistance prevention of synergistic thymol and carvacrol combinations with antibiotics in Staphylococcus aureus and Acinetobacter baumannii.

Cristina Gan, Elisa Langa, Gang Wang, Françoise Van Bambeke, Diego Ballestero, María Rosa Pino-Otín

Abstract read
In one paragraph

Article in Natural products and bioprospecting, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed.

  1. Article
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  14. Essential Oils from Wild AlbanianMolecules (Basel, Switzerland) · 2025
    Article
  15. Modulation of Antimicrobial Resistance inAntibiotics (Basel, Switzerland) · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Cristina GanUniversidad San Jorge. Campus Universitario Villanueva de Gállego Autovía A, 23 Zaragoza-Huesca, Km. 510, 50830, Villanueva de Gállego, Saragossa, Spain.
Elisa LangaUniversidad San Jorge. Campus Universitario Villanueva de Gállego Autovía A, 23 Zaragoza-Huesca, Km. 510, 50830, Villanueva de Gállego, Saragossa, Spain.
Gang WangLouvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.
Françoise Van BambekeLouvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.
Diego BallesteroUniversidad San Jorge. Campus Universitario Villanueva de Gállego Autovía A, 23 Zaragoza-Huesca, Km. 510, 50830, Villanueva de Gállego, Saragossa, Spain.
María Rosa Pino-OtínUniversidad San Jorge. Campus Universitario Villanueva de Gállego Autovía A, 23 Zaragoza-Huesca, Km. 510, 50830, Villanueva de Gállego, Saragossa, Spain. rpino@usj.es.ORCID http://orcid.org/0000-0002-3186-1722

Funding

Departamento de Ciencia, Universidad y Sociedad del Conocimiento T67-23R
6 · The paper itself

Abstract

The use of natural products as antibiotic adjuvants to enhance efficacy and mitigate resistance is increasingly recognized as a promising strategy. This study explored five novel synergistic antimicrobial combinations (SACs) of carvacrol (CARV) and three already identified SACs of thymol (THY) with chloramphenicol, gentamicin, and streptomycin against Staphylococcus aureus and Acinetobacter baumannii, critical WHO-listed pathogens, and investigated their mechanisms of action and resistance-prevention capabilities. Despite being isomers, CARV and THY exhibited distinct synergistic effects and fractional inhibitory concentration index (FICI) values depending on the antibiotic and bacterial species. The SACs significantly reduced the required antibiotic dose by 4- to 16-fold, with FICI values ranging from 0.25 to 0.5. Growth kinetics revealed that SACs completely inhibited planktonic bacterial growth, outperforming antibiotics alone. Additionally, the SACs demonstrated efficacy in both inhibiting and eradicating biofilms of S. aureus and A. baumannii. Resistance development studies highlighted that neither THY nor CARV induced resistance in these pathogens. Moreover, SACs combining aminoglycosides with THY reduced the emergence of resistance in A. baumannii by up to 32-fold. In S. aureus, THY mitigated gentamicin resistance by 16-fold. CARV exhibited similar, albeit slightly less potent, effects.Mechanistic investigations revealed that THY and CARV exert antimicrobial action by multiple mechanisms, including bacterial membrane depolarization and disruption, efflux pump inhibition, disrupting ATP metabolism and mitigating oxidative stress induced by antibiotics. These findings highlight the potential of SACs to enhance antibiotic efficacy while preventing resistance, positioning them as strong candidates for innovative antimicrobial therapies against multidrug-resistant pathogens.

Indexed as

Acinetobacter baumanniiAntibiotic resistanceCarvacrolStaphylococcus aureusThymol

Identifiers

PMID40478408
PMCPMC12144027

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.