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

Authors

  • Anders Håkansson,

    1. Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Sölvegatan 23, SE-223 62 Lund, Sweden.,
    Search for more papers by this author
  • Malin Svensson,

    1. Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Sölvegatan 23, SE-223 62 Lund, Sweden.,
    Search for more papers by this author
  • Ann-Kristin Mossberg,

    1. Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Sölvegatan 23, SE-223 62 Lund, Sweden.,
    Search for more papers by this author
  • Hemant Sabharwal,

    1. Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Sölvegatan 23, SE-223 62 Lund, Sweden.,
    Search for more papers by this author
    • Sara Linse,

      1. Department of Physical Chemistry II, Lund Institute of Technology, Lund University, Box 124, SE-221 00 Lund, Sweden.,
      Search for more papers by this author
    • Irene Lazou,

      1. Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Sölvegatan 23, SE-223 62 Lund, Sweden.,
      Search for more papers by this author
      • Bo Lönnerdal,

        1. Department of Nutrition, University of California, Davis, CA 95616, USA.
        Search for more papers by this author
      • Catharina Svanborg

        1. Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Sölvegatan 23, SE-223 62 Lund, Sweden.,
        Search for more papers by this author

      Catharina Svanborg, E-mail Catharina.Svanborg@mig.lu.se; Tel. (+46) 46 173282; Fax (+46) 46 137468.

      Abstract

      This study describes an α-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 α-lactalbumin, but native α-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 α-lactalbumin from human milk whey, but fluctuating tertiary structure. Native α-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 α-lactalbumin is a new example of naturally occurring molecules with antimicrobial activity.

      Ancillary