The Fungicidal Effect of Apolactoferrin on Aspergillus fumigatus

Lee, Kkot Sil; Chang, Kyung Hee; Kim, Myung Soo; Kim, Young Keun; Kim, Ja Kyung; Choi, Seung Hee; Huh, Ae Jung; Yeom, Joon Sup; Song, Young Goo; Kim, June Myung

Abstract

BACKGROUND: The incidence of aspergillosis is rising with the increased use of antimicrobial agents and immunosuppressive drugs for the treatment of malignant diseases, acquired immunodeficiency syndrome, or organ transplant recipients. However, treatment failures are also increasing which brings up the need for the development of new and more effective agents and/or compounds which support the activity of common antifungal agents. Apolactoferrin is one of the nonspecific host defence factors present in saliva that exhibit antifungal activity. We studied the in vitro antifungal effect of apolactoferrin in combination with amphotericin-B against Aspergillus fumigatus. METHODS: Preparation of the inoculum and the growth conditions used were those recommended by the National Committee for Clinical Laboratory Standards M38-P (Conidium-forming filamentous fungi: proposed standard). Aspergillus fumigatus test inoculum was prepared to a concentration of 0.4 X 104~5 X 104 cells/mL. Appropriate concentrations of the antifungal agents were added to the wells (50 microliter) and after inoculation, plates were incubated for 48 h at 35Celsius. Turbidity measurement was performed at 48 h at 630 nm and the MIC was defined as the lowest concentration of antifungal agents that inhibited growth of the organism as detected visually. RESULTS: In the combination of experiments, we observed a pronounced cooperative activity against growth of Aspergillus fumigatus by using apolactoferrin and amphotericin-B. The MIC of amphotericin-B was reduced by 1/10 in the presence of apolactoferrin. CONCLUSION: The combined use of apolactoferrin and amphotericin-B against severe infections with Aspergillus fumigatus is an attractive therapeutic option. Clinical studies to further elucidate the potential utility of this combination therapy have been initiated.