Modulation of drug resistance in Staphylococcus aureus by 132-hydroxy-(132-R/S)-pheophytin isolated from Sargassum polyceratium.

Efflux pumps are integral parts of the bacterial plasma membrane that are responsible for many cases of antibiotic resistance. Modulators of drug resistance are regarded as the most suitable new antibacterial therapies. We evaluated the extracts of Sargassum polyceratium and the isolated compound pheophytin (Sp-1) for antibiotic modifying activity in strains of Staphylococcus aureus with efflux pump. The minimum inhibitory concentrations (MICs) for norfloxacin, tetracycline and erythromycin were determined by the microdilution broth method, in the absence and presence of the extract at a sub-inhibitory concentration (MIC/4). The extracts and isolated compounds showed no significant antimicrobial activity, but they changed the antibiotic activity, decreasing bacterial resistance by 2 to 4x. Using a checkerboard method, it was also possible to observe the synergistic effect (ΣFIC ≤ 0.5) between Sp-1 and the antibiotics erythromycin and norfloxacin. The results indicate that the seaweed Sargassum polyceratium and pheophytin are potential sources of an antibiotic adjuvant that modulates bacterial resistance, acting as a putative efflux pump inhibitor.

Dolastane diterpenes from Canistrocarpus cervicornis and their effects in modulation of drug resistance in Staphylococcus aureus.

One new diterpene (4R,7R,14S)-4α,7α-diacetoxy-10-one-14α-hydroxydolasta-1(15),8-diene (1), and five known compounds (4R,7R,14S)-4α,7α-diacetoxy-14α-hydroxydolasta-1(15),8-diene (2), (4R,14S)-4α,14α-dihydroxydolasta-1(15),8-diene (3), (4S,9R,14S)-4α-acetoxy-9ß,14α-dihydroxydolasta-1(15),7-diene (4), 4-acetoxy-14-hydroxydolasta-1(15),7,9-triene (5) and isolinearol (6), were isolated from Canistrocarpus cervicornis. In this study, dolastane diterpenes were isolated from the alga C. cervicornis and evaluated as modifiers of antibiotic activity in Staphylococcus aureus: SA-1199B, which overexpresses the norA gene RN-4220, which encodes for the protein efflux of macrolides (MRSA), and IS-58 which has the gene encoding the protein TetK. The minimum inhibitory concentrations (MICs) for norfloxacin, tetracycline and erythromycin were determined by the microdilution broth nutrient in the absence and presence of diterpenes at a sub-inhibitory concentration (MIC/4). The extracts of C. cervicornis and isolated diterpenes showed no antibacterial activity, but showed modulatory activity, decreasing the MIC of antibiotics by 4-256 fold. The results indicate that seaweed extracts and diterpenes are potential sources of antibiotic adjuvant, acting as potential inhibitors of efflux pump.