Type

Journal Article

Authors

R Paul Ross
Colin Hill
Paul D. Cotter
Paula M. O'Connor
Des Field

Subjects

Biochemistry

Topics
antibiosis nisin anti bacterial agents chemistry drug effects genetic engineering gram positive bacteria genetics mutagenesis site directed pharmacology metabolism

The generation of nisin variants with enhanced activity against specific gram-positive pathogens. (2008)

Abstract Nisin is the prototype of the lantibiotic group of antimicrobial peptides. It exhibits broad spectrum inhibition of gram-positive bacteria including important food pathogens and clinically relevant antibiotic-resistant bacteria. Significantly, the gene-encoded nature of nisin means that it can be subjected to gene-based bioengineering to generate novel derivatives. Here, we take advantage of this to generate the largest bank of randomly mutated nisin derivatives reported to date, with the ultimate aim of identifying variants with enhanced bioactivity. This approach led to the identification of a nisin-producing strain with enhanced bioactivity against the mastitic pathogen Streptococcus agalactiae resulting from an amino acid change in the hinge region of the peptide (K22T). Prompted by this discovery, site-directed and site-saturation mutagenesis of the hinge region residues was employed, resulting in the identification of additional derivatives, most notably N20P, M21V and K22S, with enhanced bioactivity and specific activity against gram-positive pathogens including Listeria monocytogenes and/or Staphylococcus aureus. The identification of these derivatives represents a major step forward in the bioengineering of nisin, and lantibiotics in general, and confirms that peptide engineering can deliver derivatives with enhanced antimicrobial activity against specific problematic spoilage and pathogenic microbes or against gram-positive bacteria in general.
Collections Ireland -> University College Cork -> PubMed

Full list of authors on original publication

R Paul Ross, Colin Hill, Paul D. Cotter, Paula M. O'Connor, Des Field

Experts in our system

1
R Paul Ross
Teagasc
Total Publications: 441
 
2
Colin Hill
University College Cork
Total Publications: 351
 
3
Paul D. Cotter
Teagasc
Total Publications: 253
 
4
Paula M. O'Connor
Teagasc
Total Publications: 85
 
5
Des Field
Teagasc
Total Publications: 30