Enhanced Anti-Candida Activity of Neutrophils and Azole Antifungal Agents in the Presence of Lactoferrin-Related Compounds

  • Hiroyuki Wakabayashi
  • Takafumi Okutomi
  • Shigeru Abe
  • Hirotoshi Hayasawa
  • Mamoru Tomita
  • Hideyo Yamaguchi
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 443)


We investigated the effects of lactoferrin (Lf)-related compounds on growth inhibition of Candida albicans by neutrophils or antifungal agents in vitro. Human neutrophils partially inhibited the growth of C. albicans. The growth inhibition caused by human neutrophils was augmented by the addition of human Lf at concentrations which did not show any inhibitory effect in the absence of neutrophils. Similar observations were obtained also with the following combinations: human neutrophils + bovine Lf, murine neutrophils + bovine Lf, and murine neutrophils + iron saturated bovine Lf, but not in the case of murine neutrophils + human transferrin. The minimum inhibitory concentration (MIC) of azole antifungal agents, clotrimazole, ketoconazole, fluconazole, and itraconazole was reduced by 1/4 to 1/16 in the presence of a sub-MIC level of each of bovine Lf, bovine Lf pepsin hydrolysate, and the antimicrobial peptide “lactoferricin® B” (Lfcin B). Other types of antifungal agents, amphotericin B, nystatin, and flucytosine did not show such combined effects with these Lf-related compounds. The anti-Candida activity of bovine Lf or Lfcin B in combination with clotrimazole was shown to be synergistic by checkerboard analysis. Clinically isolated azole-resistant C. albicans strains were more susceptible to bovine Lf or Lfcin B than azole-susceptible strains. Trailing growth of an azole-resistant strain in the presence of fluconazole was reduced by the addition of sub-MIC levels of bovine Lf or Lfcin B. These results suggest that Lf-related compounds even at relatively low concentrations may function as an antifungal effector in combination with neutrophils thereby modulating azole antifungal efficacies in vivo.


Antifungal Agent Human Neutrophil Cefpodoxime Proxetil Human Transferrin Fractional Inhibitory Concentration Index 
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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Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Hiroyuki Wakabayashi
    • 1
  • Takafumi Okutomi
    • 2
  • Shigeru Abe
    • 2
  • Hirotoshi Hayasawa
    • 1
  • Mamoru Tomita
    • 1
  • Hideyo Yamaguchi
    • 2
  1. 1.Nutritional Science LaboratoryMorinaga Milk Industry Co., Ltd.Zama, Kanagawa 228Japan
  2. 2.Department of Microbiology and ImmunologyTeikyo University School of MedicineItabashi-ku, Tokyo 173Japan

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