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

Rafael Pereira Da Cruz,Adriano Antunes De Souza Araújo,Henrique Douglas Melo Coutinho,Marcello Iriti,Fábia Ferreira Campina,José Pinto De Siqueira Júnior,Antonia Thassya Lucas Dos Santos,Maria Do Socorro Costa,Lucindo José Quintans-Júnior,Thiago Sampaio De Freitas,Maria Flaviana Bezerra Morais-Braga,José Weverton Almeida Bezerra,Elena Maria Varoni,Irwin Rose Alencar De Menezes,Raimundo Luiz Silva Pereira

doi:10.3390/antibiotics9010028

Rafael Pereira Da Cruz, Adriano Antunes De Souza Araújo + Show 13 more

Open Access

https://doi.org/10.3390/antibiotics9010028

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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.

Highlights

Bacterial resistance to chemotherapy represents a serious problem for human health.The indiscriminate use of antibiotics for the treatment of infections has enabled the emergence of mechanisms of resistance between various microbial strains, allowing the survival and spread of pathogenic bacteria
In view of the above, the present study aims to evaluate the effect of the α-Bisabolol and β-Cyclodextrin natural compounds, both in isolation and through inclusion complexes, as inhibitors against Staphylococcus aureus strains carrying genes encoding an active efflux mechanism
The positive control inhibited both strains at the 128 μg/mL concentration

Summary

Introduction

The indiscriminate use of antibiotics for the treatment of infections has enabled the emergence of mechanisms of resistance between various microbial strains, allowing the survival and spread of pathogenic bacteria. This problem has been aggravated, especially in hospital environments, and is directly related to high mortality numbers and medical expenses, reinforcing the inefficiency and limitations of the use of certain drugs [1,2]. The mechanisms enabling bacterial cells to resist the action of chemotherapeutic agents include:. Efflux pumps have an important role in the emergence of multiple drug resistant (MDR) bacterial strains. Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus are bacteria of medical interest that use this survival strategy [4,5]

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