Bioengineered nisin derivatives with enhanced activity in complex matrices.
Bottom Line: Nisin A is the best known and most extensively characterized lantibiotic.We have previously demonstrated that bioengineering of the hinge region of nisin A can result in the generation of variants with enhanced anti-microbial activity against Gram-positive pathogens.In the case of two variants, which contain the residues SVA and NAK, respectively, within the hinge region, we demonstrate that this enhanced trait enables the peptides to dramatically outperform nisin A with respect to controlling Listeria monocytogenes in commercially produced chocolate milk that contains carrageenan as a stabilizer.
Affiliation: Department of Microbiology Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.Show MeSH
Mentions: As a result of their gene encoded nature, lantibiotics, including nisin A and nisin Z, have been the focus of bioengineering with a view to elucidating structure function relationships (Cotter et al., 2005b; Lubelski et al., 2008; Cortés et al., 2009; Field et al., 2010b). In recent years, there has been further progress, resulting in the identification of changes that significantly improve specific activity against target cells (Cortés et al., 2009; Field et al., 2010b). While some enhancements have related to rings A and B of the peptide (Fig. 1; Rink et al., 2007), the majority of enhanced peptides have resulted as a consequence of manipulation of the hinge region. The hinge comprises residues 20 (Asn), 21 (Met) and 22 (Lys) (Fig. 1), which are thought to permit the movement of the N‐ and C‐termini relative to one another during pore formation. The first success in this regard related to the creation of nisin derivatives, N20K and M21K, with enhanced anti‐microbial activity against Gram‐negatives (Yuan et al., 2004). Subsequent investigations have further highlighted the benefits of manipulating the hinge and finally resulted in the identification of nisin derivatives, such as nisin N20P, M21V, K22T and K22S, which possess enhanced specific activity against Gram‐positive pathogens (Field et al., 2008). Indeed, the enhanced specific activity of nisin M21V (or nisin V) against a wide range of food and clinical Gram‐positive pathogens has been highlighted (Field et al., 2010a).
Affiliation: Department of Microbiology Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.