A folding variant of alpha-lactalbumin with bactericidal activity against Streptococcus pneumoniae

This study describes an alpha-lactalbumin folding variant from human milk w ith bactericidal activity against antibiotic-resistant and -susceptible str ains of Streptococcus pneumoniae. The active complex precipitated with the casein fraction at pH 4.6 and was purified from casein by a combination of anion exchange and gel chromatography, Unlike other casein components, the active complex was retained on the ion-exchange matrix and eluted only with high salt. The eluted fraction showed N-terminal and mass spectrometric id entity with human milk alpha-lactalbumin, but native alpha-lactalbumin had no bactericidal effect. Spectroscopic analysis demonstrated that the active form of the molecule was in a different folding state, with secondary stru cture identical to alpha-lactalbumin from human milk whey, but fluctuating tertiary structure. Native alpha-lactalbumin could be converted to the acti ve bactericidal form by ion-exchange chromatography in the presence of a co factor from human milk casein, characterized as a C18:1 fatty acid. Analysi s of the antibacterial spectrum showed selectivity for streptococci; Gram-n egative and other Gram-positive bacteria were resistant. The folding varian t of alpha-lactalbumin is a new example of naturally occurring molecules wi th antimicrobial activity.