title: Extensive manipulation of caseicins A and B highlights the tolerance of these antimicrobial peptides to change.
abstract: 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.
authors.affiliation: Microbiology Department, University College Cork, Cork, Ireland.
authors.forename: Sarah
authors.initials: S
authors.lastname: Norberg
authors.forename: Paula M
authors.initials: PM
authors.lastname: O'Connor
authors.forename: Catherine
authors.initials: C
authors.lastname: Stanton
authors.forename: R Paul
authors.initials: RP
authors.lastname: Ross
authors.forename: Colin
authors.initials: C
authors.lastname: Hill
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Fitzgerald
authors.forename: Paul D
authors.initials: PD
authors.lastname: Cotter
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D002364:Caseins / Q000138:chemical synthesis* / Q000737:chemistry; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D023181:Antimicrobial Cationic Peptides; D002364:Caseins; D010446:Peptide Fragments; C572873:caseicin A; C572875:caseicin B