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Synergic interaction between pomegranate extract and antibiotics against Staphylococcus aureus

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We evaluated the interaction between Punica granatum (pomegranate) methanolic extract (PGME) and antibiotics against 30 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA). Susceptibility testing of the isolates to PGME and antibiotics was performed by the broth dilution method. Synergic activity was detected between PGME and the 5 antibiotics tested, chloramphenicol, gentamicin, ampicillin, tetracycline, and oxacillin, ranging from 38% to 73%. For some isolates, PGME did not interfere with the action of any of the antibiotics tested. The bactericidal activity of PGME (0.1 × MIC) in combination with ampicillin (0.5 × MIC) was assessed using chosen isolates by time-kill assays, and they confirmed the synergic activity. Using this combination, cell viability was reduced by 99.9% and 72.5% in MSSA and MRSA populations, respectively. PGME increased the post-antibiotic effect (PAE) of ampicillin from 3 to 7 h. In addition, PGME demonstrated the potential to either inhibit the efflux pump NorA or to enhance the influx of the drug. The detection of in vitro variant colonies of S. aureus resistant to PGME was low and they did not survive. In conclusion, PGME dramatically enhanced the activity of all antibiotics tested, and thus, offers an alternative for the extension of the useful lifetime of these antibiotics.Key words: Staphylococcus aureus, antibiotic-resistance, synergy, NorA, Punica granatum.

L'interaction d'un extrait alcoolique de grenade (PGME) en combinaison avec 5 antibiotiques a été testée contre 30 isolés cliniques de Staphylococcus aureus resistants (MRSA) ou sensibles (MSSA) à la méthicilline. Les tests de susceptibilité ont été effectués selon la méthode de dilution en bouillon. Une activité synergique allant de 38 % à 73 % a été détectée entre le PGME et le chloramphénicole, la gentamicine, l'ampicilline, la tétracycline ou l'oxacilline. Pour certains isolés, il n'y a pas eu d'interaction entre le PGME et les antibiotiques testés. L'activité bactéricide du PGME (0,1 × MIC) en combinaison avec l'ampicilline (0,5 × MIC) a été testée contre des isolés sélectionnés en utilizant un essai de cinétique de léthalité et a confirmé le synergisme. La viabilité cellulaire a été réduite par cette combinaison en 99,9 % et 72,5 % pour les populations MSSA et MRSA, respectivement. Le PGME a accru l'effet post-antibiotique de l'ampicilline de 3 à 7 heures. En outre, le PGME a démontré un potentiel inhibiteur de la pompe d'expulsion NorA ou d'activation de la captation de l'antibiotique. La détection de colonies variantes de S. aureus résistantes in vitro au PGME a été basse et les souches détectées n'ont pas survécu. En conclusion, le PGME a accru considérablement l'activité de tous les antibiotiques testés et offert ainsi une alternative pour leur utilization à plus long terme.Mots clés : Staphylococcus aureus, résistance aux antibiotiques, synergisme, NorA, Punica granatum.

Document Type: Research Article

Publication date: July 1, 2005

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  • Published since 1954, this monthly journal contains new research in the field of microbiology including applied microbiology and biotechnology; microbial structure and function; fungi and other eucaryotic protists; infection and immunity; microbial ecology; physiology, metabolism and enzymology; and virology, genetics, and molecular biology. It also publishes review articles and notes on an occasional basis, contributed by recognized scientists worldwide.
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