Abstract
Nisin A is the most thoroughly investigated member of the lantibiotic family of antimicrobial peptides. In addition to a long history of safe use as a food antimicrobial, its activity against multi-drug resistant pathogens has resulted in a renewed interest in applying nisin as a chemotherapeutic to treat bacterial infections. The wealth of Nisin-related information that has been generated has also led to the development of the biotechnological capacity to engineer novel Nisin variants with a view to improving the function and physicochemical properties of this already potent peptide. However, the identification of bioengineered Nisin derivatives with enhanced antimicrobial activity against Gram-positive targets is a recent event. In this study, we created stable producers of the most promising derivatives of Nisin A generated to date [M21V (hereafter Nisin V) and K22T (hereafter Nisin T)] and assessed their potency against a range of drug-resistant clinical, veterinary and food pathogens. Nisin T exhibited increased activity against all veterinary isolates, including streptococci and staphylococci, and against a number of multi-drug resistant clinical isolates including MRSA, but not vancomycin-resistant enterococci. In contrast, Nisin V displayed increased potency against all targets tested including hVISA strains and the hyper-virulent Clostridium difficile ribotype 027 and against important food pathogens such as Listeria monocytogenes and Bacillus cereus. Significantly, this enhanced activity was validated in a model food system against L. monocytogenes. We conclude that Nisin V possesses significant potential as a novel preservative or chemotherapeutic compound.