Medical Microbiology and Immunology

, Volume 182, Issue 2, pp 97–105 | Cite as

Killing of Candida albicans by lactoferricin B, a potent antimicrobial peptide derived from the N-terminal region of bovine lactoferrin

  • Wayne Bellamy
  • Hiroyuki Wakabayashi
  • Mitsunori Takase
  • Kouzou Kawase
  • Seiichi Shimamura
  • Mamoru Tomita
Original Investigations


Candida albicans was found to be highly susceptible to inhibition and inactivation by lactoferricin B, a peptide produced by enzymatic cleavage of bovine lactoferrin. Effective concentrations of the peptide varied within the range of 18 to 150 μg/ml depending on the strain and the culture medium used. Its effect was lethal, causing a rapid loss of colony-forming capability. 14C-labeled lactoferricin B bound to C. albicans and the rate of binding appeared to be consistent with the rate of killing induced by the peptide. The extent of binding was diminished in the presence of Mg2+ or Ca2+ ions which acted to reduce its anticandidal effectiveness. Binding occurred optimally at pH 6.0 and killing was maximal near the same pH. Such evidence suggests the lethal effect of lactoferricin B results from its direct interaction with the cell surface. Cells exposed to lactoferricin B exhibited profound ultrastructural damage which appeared to reflect its induction of an autolytic response. These findings suggest that active peptides of lactoferrin could potentially contribute to the host defense against C. albicans.


Peptide Cell Surface Direct Interaction Candida Albicans Host Defense 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Arnold RR, Brewer M, Gauthier JJ (1980) Bactericidal activity of human lactoferrin: sensitivity of a variety of microorganisms. Infect Immun 28:893–898Google Scholar
  2. 2.
    Bellamy W, Takase M, Yamauchi K, Wakabayashi H, Kawase K, Tomita M (1992) Identification of the bactericidal domain of lactoferrin. Biochim Biophys Acta 1121:130–136Google Scholar
  3. 3.
    Bellamy W, Takase M, Wakabayashi H, Kawase K, Tomita M (1992) Antibacterial spectrum of lactoferricin B, a potent bactericidal peptide derived from the N-terminal region of bovine lactoferrin. J Appl Bacteriol 73:472–478Google Scholar
  4. 4.
    Brines RD, Brock JH (1993) The effect of trypsin and chymotrypsin on the in vitro antimicrobial and iron-binding properties of lactoferrin in human milk and bovine colostrum. Unusual resistance of human lactoferrin to proteolytic digestion. Biochim Biophys Acta 759:229–235Google Scholar
  5. 5.
    Brock JH(1980) Lactoferrin in human milk: its role in iron absorption and protection against enteric infection in newborn infants. Arch Dis Child 55:417–421Google Scholar
  6. 6.
    Bullen JJ (1981) The significance of iron in infection. Rev Infect Dis 3:1127–1138Google Scholar
  7. 7.
    Epstein JB, Truelove EL, Izutzu KT (1984) Oral candidiasis: pathogenesis and host defense. Rev Infect Dis 6:96–106Google Scholar
  8. 8.
    Hill CP, Yee J, Selsted ME, Eisenberg D (1990) Crystal structure of defensin HNP-3, an amphiphilic dimer: mechanisms of membrane permeabilization. Science 251:1481–1484Google Scholar
  9. 9.
    Kirkpatrick CH, Green I, Rich RR, Schade AL (1971) Inhibition of Candida albicans by iron-unsaturated lactoferrin: relation to host defense mechanisms in chronic muco-cutaneous candidiasis. J Infect Dis 124:539–544Google Scholar
  10. 10.
    Lehrer RI, Ganz T, Selsted ME (1991) Defensins: endogenous antibiotic peptides of animal cells. Cell 64:229–230Google Scholar
  11. 11.
    Marquis G, Montplaisir S, Garzon S, Strykowski H, Auger P (1982) Fungitoxicity of muramidase: ultrastructural damage to Candida albicans. Lab Invest 46:627–636Google Scholar
  12. 12.
    Odds FC (1987) Candida infections: an overview. Crit Rev Microbiol 15:1–5Google Scholar
  13. 13.
    Oppenheim FG, Xu GT, McMillan FM, Levitz SM, Daimond RD, Offner GD, Troxler RF (1988) Histatins, a novel family of histidine-rich proteins in human parotid secretions. Isolation, characterization, primary structure and fungistatic effects on Candida albicans. J Biol Chem 263:7472–7477Google Scholar
  14. 14.
    Palma C, Cassone A, Serbousek D, Pearson CA, Djeu JY (1992) Lactoferrin release and interleukin-1, interleukin-6, and tumour necrosis factor production by human polymorphonuclear cells stimulated by various lipopolysaccharides: relationship to growth inhibition of Candida albicans. Infect Immun 60:4604–4611Google Scholar
  15. 15.
    Palma C, Serbousek D, Torosantucci A, Cassone A, Djeu JY (1992) Identification of a mannoprotein fraction from Candida albicans that enhances human polymorphonuclear leukocyte (PMNL) functions and stimulates lactoferrin in PMNL inhibition of candidal growth. J Infect Dis 166:1103–1112Google Scholar
  16. 16.
    Reiter B (1983) The biological significance of lactoferrin. Int J Tissue React 5:87–96Google Scholar
  17. 17.
    Schröder G, Brandenburg K, Seydel U (1992) Polymyxin B induces transient permeability fluctuations in asymmetric planar lipopolysaccharide/phospholipid bilayers. Biochemistry 31:631–638Google Scholar
  18. 18.
    Selsted ME, Szklarek ED, Ganz T, Lehrer RI (1985) Activity of rabbit leukocyte peptides against Candida albicans. Infect Immun 49:202–206Google Scholar
  19. 19.
    Shepherd MG, Poulter RTM, Sullivan PA (1985) Candida albicans: biology, genetics, and pathogenicity. Ann Rev Microbiol 39:579–614Google Scholar
  20. 20.
    Storm DR, Rosenthal KS, Swanson PE (1977) Polymyxin and related peptide antibiotics. Annu Rev Biochem 46:723–763Google Scholar
  21. 21.
    Soukka T, Tenovuo J, Lenander-Lumikari M (1992) Fungicidal effect of human lactoferrin against Candida albicans. FEMS Microbiol Lett 90:223–228Google Scholar
  22. 22.
    Tomita M, Bellamy W, Takase M, Yamauchi K, Wakabayashi H, Kawase K (1991) Potent antibacterial peptides generated by pepsin digestion of bovine lactoferrin. J Dairy Sci 74:4137–4142Google Scholar
  23. 23.
    Xu T, Levitz SM, Daimond RD, Oppenheim FG (1991) Anticandidal activity of major human salivary histatins. Infect Immun 50:2549–2554Google Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • Wayne Bellamy
    • 1
  • Hiroyuki Wakabayashi
    • 1
  • Mitsunori Takase
    • 1
  • Kouzou Kawase
    • 1
  • Seiichi Shimamura
    • 1
  • Mamoru Tomita
    • 1
  1. 1.Nutritional Science Laboratory, Morinaga Milk Industry Co. Ltd.KanagawaJapan

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