Since increasing bacterial resistance to antibiotics is currently one of the biggest threats to human health, there is an urgent need of new antibacterial drugs in development. Efflux pumps represent membrane transport proteins, which eliminate toxic substrates out of the cell. This mechanism contributes to the importance of efflux pumps in bacterial antibiotic resistance as well as in chemotherapy resistance. [1], [2]
As plants show an enormous compound diversity and low toxicity, they are promising substances for new efflux pump inhibitors to combat increasing bacterial resistance. Different plants of the Artemisia species (e.g. A. scoparia, A.- annua) within the family of Asteraceae as well as some species of Scutellaria within the family of Lamiaceae are screened in order to examine a potential inhibition of efflux pumps. The respective plant parts are extracted with four solvents of varying polarity and screened on the non-pathogenic model strains Mycobacterium smegmatis mc2 155 and Escherichia coli K12 MG1655. The results showed that extracts of a Scutellaria species (MIC=8mg/l) and an Artemisia species (MIC=64mg/l) possess strong antimicrobial activities against Mycobacterium smegmatis mc2 155. Another extract of a Scutellaria species showed good resistance- modulating effects against Escherichia coli K12 (MF=8) and AG100 (MF=16). Since the human intestinal and lung epithelium are equipped with efflux pumps, another essential part of this study is to investigate the impact of potent plant inhibitors on these features. For this, standardized in-vitro models are used, which recapitulate the intestinal barrier and serve to study the permeability behaviour of drugs. Caco-2 cells are tested for the oral route and Calu-3, A549 and H441 cells for the respiratory route.
[1] Piddock LJV. Clinically relevant chromosomally encoded multidrug resistance efflux pumps in bacteria. Clin Microbiol Rev 2006; 19: 382–402. [2] Marquez B. Bacterial efflux systems and efflux pumps inhibitors. Biochimie 2005; 87:1137–1147.