Efflux pumps are proteins present in the plasma membrane of bacteria, which transport antibiotics and other compounds into the extracellular medium, conferring resistance. The discovery of natural efflux pump inhibitors is a promising alternative. α-Bisabolol is a sesquiterpene isolated from several plants such as Matricaria chamomilla L. and has important properties such as antibacterial and anti-inflammatory activity. Currently, the formation of inclusion complexes with β-Cyclodextrin has been used for improving the physicochemical characteristics of the host molecule. This study evaluated the effect of α-Bisabolol, in isolation and in complexation with β-Cyclodextrin, as TetK and NorA efflux pump inhibitors in Staphylococcus aureus strains. The minimum inhibitory concentration (MIC) was determined. Subsequently, inhibitory activity over the pumps was observed by an MIC reduction for the antibiotics, by using subinhibitory concentrations (MIC/8) in combination with tetracycline and norfloxacin. The MIC of the compounds was ≥1024 μg/mL. α-Bisabolol potentiated the action of tetracycline and reduced the MIC of norfloxacin to a clinically relevant concentration. The complexed substance showed synergism however, the effect of the isolated α-Bisabolol was superior to the complex. These results indicate α-Bisabolol is a potential substance to be used as an efflux pump inhibitor.

Background: Phytol is a diterpene from the long-chain unsaturated acyclic alcohols, known for its diverse biological effects, including antimicrobial and anti-inflammatory activities. Present in essential oils, phytol is a promising candidate for various applications in the pharmaceutical and biotechnological sectors. This study aimed to evaluate the in vitro antibacterial and drug-potentiating effects of phytol against multidrug-resistant bacteria and to evaluate its in silico properties: ADME and molecular docking. Methods: The in vitro antibacterial activity of phytol and the phytol combined with conventional drugs was evaluated by microdilution tests against standard and resistant bacterial strains. Finally, the SwissADME platform was employed to analyse the physicochemical and pharmacokinetic characteristics of phytol. Results: Phytol significantly reduced the Minimum Inhibitory Concentration (MIC) of norfloxacin and gentamicin required to inhibit multidrug-resistant strains of Escherichia coli and Staphylococcus aureus, respectively. Additionally, ADME analysis revealed that phytol exhibits low toxicity and favourable pharmacokinetic properties; in addition, it is revealed through molecular docking that phytol showed a relevant affinity with the proteins 6GJ1 and 5KDR, however, with values lower than the drugs gentamicin and ampicillin. Conclusions: Collectively, these findings suggest that phytol holds potential as an effective adjuvant in combating antimicrobial resistance.

Mesosphaerum suaveolens (L.) Kuntze is a species widely used traditionally in the treatment of ailments, such as stomach pain, hemorrhoids, cough, verminosis, ulcer, liver disease, fever, influenza, nasal congestion, and inflammation. This review aims to provide a survey of available information on seven international electronic databases (Google Scholar, Medline, ResearchGate, Web of Science, Scopus, Science Direct, and PubMed) about botanical aspects, traditional uses, phytochemistry, and biological activities of M. suaveolens. Mesosphaerum suaveolens is a tropical America native species, but it can be found in several parts of the world as a ruderal plant. The species is the most studied species of the genus Lamiaceae due its phytochemical aspect, especially regarding the chemical composition of its essential oil. Besides the essential oils, M. suaveolens is a source of numerous secondary compounds such as triterpenes, diterpenes, and phenolic compounds, which are related to its biological activities, such as allelopathic, antibacterial, antifungal, insecticidal, and larvicidal activities as described in the literature.

Infections by multiresistant microorganisms have led to a continuous investigation of substances acting as modifiers of this resistance. By following this approach, the chemical composition of the essential oil from Piper caldense leaf and its antimicrobial potential were investigated. The antimicrobial activity was determined by broth microdilution method providing values for minimum inhibitory concentration (MIC), IC₅₀, and minimum fungicidal concentration (MFC). The essential oil was tested as a modulator for several antibiotics, and its effect on the morphology of Candida albicans (CA) strains was also investigated. The chemical characterization revealed an oil composed mainly of sesquiterpenes. Among them are caryophyllene oxide (13.9%), spathulenol (9.1%), δ-cadinene (7.6%) and bicyclogermacrene (6.7%) with the highest concentrations. The essential oil showed very low activity against the strains of CA with the lowest values for IC₅₀ and MFC of 1790 μg/mL and 8192 μg/mL, respectively. The essential oil modulated the activity of fluconazole against CA URM 4387 strain, which was demonstrated by the lower IC₅₀ obtained, 2.7 μg/mL, whereas fluconazole itself presented an IC₅₀ of 7.76 μg/mL. No modulating effect was observed in the MFC bioassays. The effect on fungal morphology was observed for both CA INCQS 40006 and URM 4387 strains. The hyphae projection was completely inhibited at 4096 μg/mL and 2048 μg/mL, respectively. Thus, the oil has potential as an adjuvant in antimicrobial formulations.

The emergence of fungal resistance to commercial drugs has been a major problem for the WHO. In this context, research with natural products is promising in the discovery of new active substances. Thus, this work evaluated the antifungal effect of a medicinal plant (i.e., Mesosphaerum suaveolens) against strains of the genus Candida, tested the combined effect with the drug fluconazole, and, finally, determined the phenolic constituents present in the species. Initially, aqueous extracts of leaves (AELMs) and aerial parts (AEAPMs) of the species were prepared. For microbiological assays, the minimum fungicidal concentration was determined by broth microdilution, and the combined effect of fluconazole extracts were verified by sub-inhibitory microdilution concentrations (CFM/8) followed by spectrophotometric readings which were used to determine the IC₅₀. HPLC detected the presence of flavonoids and phenolic acids, detecting eight compounds present in the samples of which caffeic acid and quercetin were major components. The AELMs modulated fluconazole activity since it decreased fluconazole’s IC₅₀ from 7.8 µg/mL to an IC₅₀ of 4.7 µg/mL (CA LM 77) and from 28.8 µg/mL to 18.26 µg/mL (CA INCQS 40006) for the C. albicans strains. The AEAPMs were able to potentiate the effect of fluconazole more effectively than the AELMs. Such an effect was significant for the 16 µg/mL concentration for CA LM 77 and 32 µg/mL for CA INCQS 40006. The AEAPMs as well as the AELMs presented clinically relevant activities for C. tropicalis strains. For the C. tropicalis LM 23 strain, the AEPMs obtained an IC₅₀ of 25 µg/mL and the AELMs an IC₅₀ of 359.9 µg/mL.

The aim of this study was to identify and evaluate the chemical compositions and effects of the S. tuberosa leaf and root hydroalcoholic extracts (HELST and HERST) against different strains of Candida. Chemical analysis was performed by Ultra-Performance Liquid Chromatography Coupled to Quadrupole/Time of Flight System (UPLC-MS-ESI-QTOF). The Inhibitory Concentration of 50% of the growth (IC₅₀₎ as well as the intrinsic and combined action of the extracts with the antifungal fluconazole (FCZ) were determined by the microdilution method while the minimum fungicidal concentrations (MFCs) and the effect on fungal morphological transitions were analyzed by subculture and in humid chambers, respectively. From the preliminary phytochemical analysis, the phenols and flavonoids were the most abundant. The intrinsic IC₅₀ values for HELST ranged from 5716.3 to 7805.8 µg/mL and from 6175.4 to 51070.9 µg/mL for the HERST, whereas the combination of the extracts with fluconazole presented IC₅₀ values from 2.65 to 278.41 µg/mL. The MFC of the extracts, individually, for all the tested strains was ≥16384 µg/mL. When fluconazole was combined with each extract, the MFC against CA URM 5974 was reduced (HELST: 2048 and HERST: 4096 µg/mL). Synergism was observed against standard C. albicans (CA) and C. tropicalis (CT) strains and with the root extract against the CT isolate. The leaf extract inhibited the morphological transition of all strains while the root extract inhibited only CT strains.