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

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 ß-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 ß-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.

Photoinduced Antibacterial Activity of the Essential Oils from Eugenia brasiliensis Lam and Piper mosenii C. DC. by Blue Led Light.

The objective of this work was to evaluate the phytochemical composition and the antibacterial and antibiotic-modulating activities of the essential oils of Eugenia brasiliensis Lam (OEEb) and Piper mosenii C. DC (OEPm) singly or in association with blue LED (Light-emitting diode) light. The antibacterial and antibiotic-modulatory activities of the essential oils on the activity of aminoglycosides were evaluated to determine the minimum inhibitory concentration (MIC, µg/mL) in the presence or absence of exposure to blue LED light. The chemical analysis showed α-pinene and bicyclogermacrene as major constituents of OEPm, whereas α-muurolol was the main compound of OEEb. Both OEEb and OEPm showed MIC ≥ 512 µg/mL against the strains under study. However, the association of these oils with the blue LED light enhanced the action of the aminoglycosides amikacin and gentamicin. In conclusion, the association of aminoglycosides with the blue LED light and essential oils was effective against resistant bacteria.

Avaliações comparativas da associação entre antibióticos frente à Pseudomonas aeruginosa / Evaluación comparativa del uso asociado de antibióticos frente a Pseudomonas aeruginosa / Evaluation of the association antibiotics against Pseudomonas aeruginosa

Introdução: Pseudomonas aeruginosa caracteriza-se como bastonete gram-negativo reto ou ligeiramente curvo, aeróbio estrito, podendo ser encontrado na água, solo, vegetais, esgoto e animais. É um patógeno nosocomial com envolvimento em infecções hospitalares provocando infecções oportunistas em pacientes, principalmente naqueles imunocomprometidos. Uma das características de P. aeruginosa é seu alto nível de resistência intrínseca a agentes antimicrobianos estruturalmente diferentes. Objetivo: avaliar as atividades microbiológicas e comparar as atividades decorrentes da associação entre antibióticos que atuam no mesmo alvo e também em alvos diferentes frente às cepas bacterianas de Pseudomonas aeruginosa. Métodos: a Concentração Inibitória Mínima (CIM) foi realizada pelo método de microdiluição em caldo. Foi realizada modulação com bactérias associando os antibióticos. Resultados: as associações claritromicina‒imipenem e claritromicina ‒ciprofloxacina apresentaram sinergismo frente à P. aeruginosa, porém a associação claritromicina‒gentamicina demonstrou indiferença. Por outro lado as associações imipenem‒claritromicina, ciprofloxacino‒claritromicina e gentamicina ‒claritromicina apresentaram antagonismo. Conclusão: o resultado deste ensaio sugere que a associação de dois antibióticos testados aumenta o seu potencial antimicrobiano, podendo ser usado em combinação mediante investigações posteriores que comprovem a segurança de tal uso(AU)

Introduction: Pseudomonas aeruginosa is an anaerobic and gramnegative rod, they can be isolated from water, soil, vegetables, waste and animals. This microorganism is a nosocomial opportunistic infectious agent, mainly for immunocompromised patients. One of the main traits of P. aeruginosa is its intrinsic drug resistance to structurally different antibiotics. Objective: to evaluate the microbiological effect and to compare the activities derived from the antibiotic association s acting on the same target and on different targets against P. aeruginosa strains. Methods: the Minimun Inhibitory Concentration (MIC) was determined by broth microdilution method. The modulation of the activity on the bacteria was based on the antibiotic association. Results: the association of clarithromycin-imipenem and of clarothromycin-ciprofloxacin demonstrate synergism against P. aeruginosa. However, the association of clarithromycin?gentamycin did not show differences. On the other hand, the association of imipenem-clarihtromycin, of ciprofloxacine-clarithromycin and of gentamycin-clarithromycin showed antagonistic effect. Conclusions: the results of this study indicated that the association of two antibiotics enhances the antimicrobial potential of these drugs, and that they can be used in combination whenever other research studies confirm the safety of such use(AU)

Introducción: la Pseudomonas aeruginosa se caracteriza por ser gramnegativos con imagen de bastones rectos o ligeramente curvos, aeróbios, se pueden encuentrar en el agua, el suelo, en plantas, animales y aguas residuales. Es un patógeno nosocomial implicado en infecciones hospitalarias, causando infecciones oportunistas en pacientes, especialmente en aquellos inmunocomprometidos. Una de las características de la P. aeruginosa es su alto nivel de resistencia intrínseca a agentes antimicrobianos estructuralmente diferentes. Objetivo: evaluar las actividades microbiológicas y comparar las actividades derivadas de la asociación de antibióticos que actúan sobre la misma diana y también sobre diferentes dianas frente a cepas bacterianas de Pseudomonas aeruginosa. Métodos: el cálculo de la Concentración Mínima Inhibitoria (CMI) se realizó por el método de microdilución en caldo. La modulación de la actividad sobre bacterias se realizó por asociación de antibióticos. Resultados: las asociaciones claritromicina‒imipenem y claritromicina ‒ciprofloxacina mostraron sinergismo frente a P. aeruginosa; sin embargo la asociación claritromicina‒gentamicina no mostro diferencias. Por otro lado las asociaciones imipenem‒claritromicina, ciprofloxacino‒claritromicina y gentamicina ‒claritromicina demostraron antagonismo. Conclusión: los resultados de este estudio indican que la combinación de dos antibióticos aumenta su potencial antimicrobiano, y que pueden ser utilizadas en combinación, una vez que otras investigaciones confirmen la seguridad de dicho uso(AU)