Norberg, S,O'Connor, PM,Stanton, C,Ross, RP,Hill, C,Fitzgerald, GF,Cotter, PD

2012

January

Applied and Environmental Microbiology

Extensive Manipulation of Caseicins A and B Highlights the Tolerance of These Antimicrobial Peptides to Change

Validated

()

ENTEROBACTER-SAKAZAKII LISTERIA-MONOCYTOGENES LANTIBIOTIC LACTICIN-3147 ANTIBACTERIAL NISIN HYDROPHOBICITY MECHANISM CHARGE MILK

78

2353

2358

Caseicins A and B are low-molecular-weight antimicrobial peptides which are released by proteolytic digestion of sodium caseinate. Caseicin A (IKHQGLPQE) is a nine-amino-acid cationic peptide, and caseicin B (VLNENLLR) is a neutral eight-amino-acid peptide; both have previously been shown to exhibit antibacterial activity against a number of pathogens, including Cronobacter sakazakii. Previously, four variants of each caseicin which differed subtly from their natural counterparts were generated by peptide synthesis. Antimicrobial activity assays revealed that the importance of a number of the residues within the peptides was dependent on the strain being targeted. In this study, this engineering-based approach was expanded through the creation of a larger collection of 26 peptides which are altered in a variety of ways. The investigation highlights the generally greater tolerance of caseicin B to change, the fact that changes have a more detrimental impact on anti-Gram-negative activity, and the surprising number of variants which exhibit enhanced activity against Staphylococcus aureus.

DOI 10.1128/AEM.07312-11