The two peptide lantibiotic lacticin 3147 acts synergistically with polymyxin to inhibit Gram negative bacteria

Abstract

Background: The emergence of bacterial drug resistance encourages the re-evaluation of the potential of existing antimicrobials. Lantibiotics are post-translationally modified, ribosomally synthesised antimicrobial peptides with a broad spectrum antimicrobial activity. Here, we focussed on expanding the potential of lacticin 3147, one of the most studied lantibiotics and one which possesses potent activity against a wide range of Gram positive species including many nosocomial pathogens. More specifically, our aim was to investigate if lacticin 3147 activity could be enhanced when combined with a range of different clinical antibiotics.

Results: Initial screening revealed that polymyxin B and polymyxin E (colistin) exhibited synergistic activity with lacticin 3147. Checkerboard assays were performed against a number of strains, including both Gram positive and Gram negative species. The resultant fractional inhibitory concentration (FIC) index values established that, while partial synergy was detected against Gram positive targets, synergy was obvious against Gram negative species, including Cronobacter and E. coli.

Conclusions: Combining lacticin 3147 with low levels of a polymyxin could provide a means of broadening target specificity of the lantibiotic, while also reducing polymyxin use due to the lower concentrations required as a result of synergy.

Figure 1

Antibiotic disc-based assessment of lacticin 3147 and polymyxin B/E sensitivity and synergy. Antibiotic discs infused with polymyxin B and polymyxin E were placed on agar plates swabbed with E. faecium DO and E. coli EC101. Lacticin 3147 (1.2, 1.9 or 2.5 μg) was added to additional discs containing the respective polymyxins and to blank, non-polymyxin containing, controls. Results are the outcome of duplicate experiments and are expressed as total area of inhibitory zone expressed in mm².