A synergy interaction of artocarpin and tetracycline against Pseudomonas aeruginosa and its mechanism of action on membrane permeability

The emergence of antibacterial resistance has significantly increased. Pseudomonas aeruginosa is associated with nosocomial infection and difficult to control. Artocarpin, a flavonoid from Artocarpus heterophyllus Lam. exhibits several pharmacological properties including antibacterial. The study was performed to evaluate interaction between artocarpin and antibiotics including tetracycline against P. aeruginosa. Its mechanism of action on membrane permeability was also investigated. Broth microdilution was conducted for the susceptibility assay. The interaction of artocarpin and antibiotics was evaluated using checkerboard method, the effect on alteration of membrane cell was investigated using bacteriolysis and the released of 260 nm materials. Artocarpin showed moderate to weak activity against the Gram-negative bacteria including P. aeruginosa with MIC values in the range of 31.25-250 mu g/mL. A synergistic effect against P. aeruginosa was produced by the combination of artocarpin (31.25 mu g/mL) and tetracycline (1.95 mu g/mL) with FICI of 0.37. The time-killing assay showed that artocarpin enhance the antibacterial activity of tetracycline against P. aeruginosa by completely inhibiting the bacterial growth. Additionally, the mixture of artocarpin (31.25 mu g/mL) and tetracycline (1.95 mu g/mL) disrupted membrane permeability and lead to cell death. These results proposed that the combination of artocarpin and tetracycline may be used to overcome P. aeruginosa infection.