Planta Med 2011; 77 - PM86
DOI: 10.1055/s-0031-1282844

Chilean medicinal plants as a source of norA efflux pump inhibitors against resistant Staphylococcus aureus strains

JG Holler 1, HC Slotved 2, SB Christensen 1, P Mølgaard 1
  • 1University of Copenhagen, Faculty of Pharmaceutical Sciences, Department of Medicinal Chemistry, Copenhagen, Denmark
  • 2Department of Microbiological Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark

Staphylococcus aureus is a highly encountered pathogen in skin infections and multidrug resistance in this strain caused by native norA effluxpump is a growing clinical problem. A path to solve this problem is the synergistic combination of an antibiotic with an effluxpump inhibitor (EPI) providing an effective drug. Ethnopharmacological knowledge on treatment of infected wounds may prove valuable in the search for anti-staphylococcal compounds.

24 plants traditionally used by the Huilliche people in southern Chile for wound healing therapy were used. Plant extracts were tested for norA effluxpump inhibitory activity in an assay based on fluorometric measurement of ethidium bromide transport by norA. Synergy studies was performed using the microtiter checkerboard method and MIC to rule out intrinsic activity

A total of 24 plant species were collected. Seven crude extracts was active (>50% inhibition) at 100µg/ml, compared to reference drug reserpine at 20µg/ml. None of the seven plants revealed antimicrobial action in the concentration range tested. The two most potent efflux inhibitors were tested for dose-response activity and showed similar profile as reserpine, but had higher IC50 -values of 11 and 14µg/ml compared to 6µg/ml of reserpine. Synergy studies of the two extracts G and M showed a 4-fold reduction in Moxifloxacin MIC at an extract concentration of 100µg/ml.

Extracts of Huilliche medicinal plants is likely to inhibit S. aureus norA facilitated EtBr efflux. Combination of extracts G and M with Moxifloxacin enhanced antibiotic action 4 fold.

Acknowledgement: Glenn W. Kaatz of John D. Dingell VA Medical Center, Detroit for encouraging help on setting up the assay. Luca Guardabassi at LIFE-faculty University of Copenhagen for hosting our experiments.