title: A folding variant of alpha-lactalbumin with bactericidal activity against Streptococcus pneumoniae.
abstract: This study describes an alpha-lactalbumin folding variant from human milk with bactericidal activity against antibiotic-resistant and -susceptible strains 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 identity 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 structure identical to alpha-lactalbumin from human milk whey, but fluctuating tertiary structure. Native alpha-lactalbumin could be converted to the active bactericidal form by ion-exchange chromatography in the presence of a cofactor from human milk casein, characterized as a C18:1 fatty acid. Analysis of the antibacterial spectrum showed selectivity for streptococci; Gram-negative and other Gram-positive bacteria were resistant. The folding variant of alpha-lactalbumin is a new example of naturally occurring molecules with antimicrobial activity.
authors.affiliation: Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Sölvegatan 23, SE-223 62 Lund, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Håkansson
authors.forename: M
authors.initials: M
authors.lastname: Svensson
authors.forename: A K
authors.initials: AK
authors.lastname: Mossberg
authors.forename: H
authors.initials: H
authors.lastname: Sabharwal
authors.forename: S
authors.initials: S
authors.lastname: Linse
authors.forename: I
authors.initials: I
authors.lastname: Lazou
authors.forename: B
authors.initials: B
authors.lastname: Lönnerdal
authors.forename: C
authors.initials: C
authors.lastname: Svanborg
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002364:Caseins / Q000737:chemistry / Q000494:pharmacology; D005591:Chemical Fractionation; D002852:Chromatography, Ion Exchange; D004352:Drug Resistance, Microbial; D005227:Fatty Acids / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007768:Lactalbumin / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D008895:Milk, Human / Q000737:chemistry; D017510:Protein Folding; D020539:Sequence Analysis, Protein; D013057:Spectrum Analysis / Q000379:methods; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D002364:Caseins; D005227:Fatty Acids; D007768:Lactalbumin