Antimicrobial, modulatory, and antibiofilm activity of tt-farnesol on bacterial and fungal strains of importance to human health.

In this study, we analyzed the antimicrobial, antibiofilm, and modulatory activities of trans-trans-farnesol (tt-farnesol). The minimum inhibitory concentration (MIC) of this sesquiterpene was evaluated against 31 Gram-positive and Gram-negative bacterial strains and 4 species of the genus Candida. Furthermore, we examined its inhibitory action on biofilm production as well as antibiotic modulation. Only Gram-positive species presented susceptibility to tt-farnesol (MIC ranging from 8 µg/mL to 128 µg/mL). No synergistic or antagonistic effects were observed between tt-farnesol (1/4 and 1/8 of MIC) and first-choice antibiotics against multidrug resistant strains. However, the modulatory action of tt-farnesol (1/2 and 1/4 of the MIC) decreased 8 × MIC of non-inhibitory ß-lactam antibiotic against a Methicillin-resistant strain. In the antibiofilm assay, tt-farnesol inhibited biofilm formation, especially in Methicillin-resistant Staphylococcus aureus (MRSA) strains, at concentrations ranging from 2 µg/mL to 128 µg/mL. Additionally, in the molecular docking study, the tt-farnesol molecule demonstrated a remarkable binding affinity with important proteins involved in the biofilm production, such as IcaA and Srt proteins. The antimicrobial action of tt-farnesol on Streptococcus pyogenes and Streptococcus agalactiae strains was evaluated for the first time, presenting an MIC of 16 µg/mL for both strains. Our findings reveal the antibacterial, antibiofilm, and modulatory potential of tt-farnesol to aid in the fight against infectious processes.

Antimicrobial activity and inhibition of the NorA efflux pump of Staphylococcus aureus by extract and isolated compounds from Arrabidaea brachypoda.

Arrabidaea brachypoda is a native shrub of the Brazilian Cerrado widely used in the folk medicine for treatment of renal diseases and articular pains. This study aimed to, first, evaluate the antimicrobial activity of both extracts and isolated molecules Brachydins BR-A and BR-B obtained from the flowers of A. brachypoda against Staphylococcus aureus, Escherchia coli and Candida albicans species. A second objective was to investigate if these natural products were able to potentiate the Norfloxacin activity against the strain Staphylococcus aureus SA1199-B that overexpress the norA gene encoding the NorA efflux pump. Extracts and isolated compounds were analyzed by HPLC-PDA and LC-ESI-MS respectively. Minimal inhibitory concentrations of Norfloxacin or Ethidium Bromide (EtBr) were determined in the presence or absence of ethanolic extract, dichloromethane fraction, as well as BR-A or BR-B by microdilution method. Only BR-B showed activity against Candida albicans. Addition of ethanolic extract, dichloromethane fraction or BR-B to the growth media at sub-inhibitory concentrations enhanced the activity of both Norfloxacin and EtBr against S. aureus SA1199-B, indicating that these natural products and its isolated compound BR-B were able to modulate the fluoroquinolone-resistance possibly by inhibition of NorA. Moreover, BR-B inhibited the EtBr efflux in the SA1199-B strain confirming that it is a NorA inhibitor. Isolated BR-B was able to inhibit an important mechanism of multidrug-resistance very prevalent in S. aureus strains, thus its use in combination with Norfloxacin could be considered as an alternative for the treatment of infections caused by S. aureus strains overexpressing norA.