Synergistic antimicrobial profiling of violacein with commercial antibiotics against pathogenic micro-organisms

Context: Chromobacterium violaceum Bergonzini (Neisseriaceae), a Gram-negative bacterium, secretes a spectacular pigment called violacein. Violacein is a quorum-sensing metabolite and is also an active antimicrobial, anticancer agent. However, its efficiency as a potential drug, alone or in synergy with other active principles, has not being completely exploited. With the advent of different multi-drug resistant strains, it becomes essential to find a new natural product(s) that could be effectively used as a therapeutic agent. Objective: This work focused on the extraction of violacein from an isolated strain of C. violaceum and determined the combinatory effect of violacein with commercial antibiotics against various pathogens. Materials and methods: Violacein production was optimized and was later extracted using ethanol and characterized by liquid chromatography-mass spectrometry and infrared spectroscopy. Then, individual minimum inhibitory concentration (MIC) values for each of the antibiotics were determined followed by violacein-commercial antibiotics (1: 1) combinations, tested at different concentrations starting from 500 to 1 mu g/ml against major pathogens. Results and discussion: The individual MIC data for violacein was found to be 5.7 mu g/ml (Staphylococcus aureus), 15.6 mu g/ml (Klebsiella pneumoniae), 18.5 mu g/ml (Pseudomonas aeruginosa), 20.0 mu g/ml (Vibrio cholerae) and 5.7 mu g/ml (Salmonella typhi). Violacein-gentamicin and violacein-cefadroxil combinations had MIC of 1.0 mu g/ml against S. aureus. Most violacein-macrolide and violacein-aminoglycoside class combinations revealed fractional inhibitory concentration indices (FICI) of <0.5, thus exhibiting synergism. Furthermore, violacein-azithromycin and violacein-kanamycin combination, exhibited significant synergy (FICI-0.3) against S. typhi. Conclusion: Violacein works synergistically with most commercial antibiotics and could be used as drug in combination with other antimicrobial agents.