Effect of α-Bisabolol and Its β-Cyclodextrin Complex as TetK and NorA Efflux Pump Inhibitors in Staphylococcus aureus Strains

Abstract

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.

Antibacterial potential of selected phytomolecules: An experimental study

“…Natural monocyclic sesquiterpene alcohol (α‐bisabolol) and its β‐cyclodextrin complex exhibited their inhibitory potential against TetK and NorA efflux pump of S. aureus . Also, α‐bisabolol enhanced the inhibitory action of tetracycline and decreased the MIC of norfloxacin to a clinically relevant concentration showing a synergistic effect with SABX 35 . In a different study, involving molecular docking and in vitro assays, to analyze inhibition of the efflux pump of resistant strains of S. aureus SA1119B and K2068 showing resistance to norfloxacin and ciprofloxacin, the essential oil of Ocotea odorífera and safrole presented promising antibacterial and antibiotic‐enhancing properties by inhibiting the efflux pumps 36 .…”

Dynamic Boolean modelling reveals the influence of energy supply on bacterial efflux pump expression

“…Efflux pumps are capable of transporting a range of substances from the cell compartment to the extracellular medium, reducing intracellular accumulation of substances including antibiotics, and thus conferring resistance. Their central role in facilitating clinically relevant AMR makes efflux pumps an attractive drug target, with much research directed at efflux pump inhibitors as a novel therapeutic to overcome efflux-mediated resistance [6][7][8][9][10].…”

Health Benefits, Pharmacological Effects, Molecular Mechanisms, and Therapeutic Potential of α-Bisabolol

“…In digging into the antibacterial mechanisms associated with α-Bisabolol, α-Bisabolol was tested for a potential inhibition of TetK and NorA efflux pump responsible for pumping out antibiotics into extracellular space and thus rendering the bacteria resistant to the administered antibiotic. The combination of α-Bisabolol with tetracycline and norfloxacin resulted in potentiation of their action, illustrated by a reduction in their minimum inhibitory concentration (MIC) from 192 µg/mL to 128 µg/mL against SA IS-58 TetK pump expressing strain and from 256 μg/mL to 32 μg/mL against SA 1199 B NorA pump expressing strain, respectively [ 98 ].…”