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Antibacterial activity of Celastrol against Bacillus subtilis
Celastrol, a nortriterpene methylene quinone isolated from the root bark of members of the Celastraceae family, has shown promise as an anti-inflammatory, antioxidant and antiproliferative against several cancer cell lines . Furthermore, in a previous work , celastrol showed antimicrobial activity against Gram-positive bacteria, but its mechanism of action has not been described. With this in mind, we have studied the antibacterial properties of the quinone against Bacillus subtilis. The killing curves show that celastrol, added at lag phase of growth, at 3µg/mL (3 x MIC) exhibited a bactericidal effect (≥3 log10 in CFU/mL reduction) after 7h of treatment and bacteriostatic activity when it was applied to growing cells. Moreover, the bactericidal effect was dependent on the starting inoculum, the lower the inoculum size (≤106 CFU/mL) the greater the decrease in CFU/mL (≥3 log10), whereas bacteriostatic activity was observed at a higher inoculum (107 CFU/mL). In addition, the antibacterial activity was affected by the composition of the medium, showing a bactericidal effect when the medium had yeast extract and a bacteriostatic effect when there was a lack of this component. For other related compounds, functional injury to the membrane has been reported as a mechanism of action . The effect of celastrol was determined by both the leakage of the cellular constituents absorbing at 260nm and membrane damage using the BacLight assay. The results obtained showed no leakage of cellular constituents and an absence of damage in the cell membrane.
Acknowledgements: This study was supported by the DGES (CTQ2006–13376-BQU). PMN thanks to Caja Canarias for a fellowship
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