Synergistic Antifungal Effect of Lactoferrin with Azole Antifungals against Candida albicans and a Proposal for a New Treatment Method for Invasive Candidiasis
Open accessAbstract
The combination of lactoferrin with fluconazole has been reported to synergistically enhance the antifungal activity of fluconazole against Candida spp. and inhibit the hyphal formation in fluconazole-resistant strains of Candida albicans. In this study, we investigated the association between the therapeutic effects of this combination and the pharmacological characteristics of fluconazole and itraconazole and the variation in these effects with differences among the strains in terms of the susceptibility and resistance mechanisms. Lactoferrin enhanced the growth-inhibitory activity of fluconazole against two different ergosterol mutants but not againt pump mutants or an azole-susceptible strain; but increased the activity of itraconazole against all the strains tested in this study. Exogenous iron cancelled the synergistic effect, which suggests that the iron-chelating function of lactoferrin may contribute to the synergism. Besides, radiolabeled fluconazole assays revealed that lactoferrin did not affect the intracellular concentrations of fluconazole, thereby indicating that these synergistic effects were not due to the alteration of the intracellular uptake of the drug. The development of new clinical treatments and therapeutic method against resistant Candida will depend on our understanding of the resistance mechanisms and methods to overcome them by the application of suitable drug combinations with synergistic effects. The results of this study might contribute to the improvement of our understand of the mechanisms underlying the resistance of Candida strains.
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Iron homeostasis has been regarded as a potential target for other azole chemosensitizing agents such as doxycycline and lactoferrin.
“Notably, iron homeostasis has been regarded as a potential target for other azole chemosensitizing agents such as doxycycline and lactoferrin [65,66].”
From Aprepitant, an antiemetic agent, interferes with metal ion homeostasis of<i>Candida auris</i>and displays potent synergistic interactions with azole drugs (2020) · cites this paper as [66]
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- Authors
- Kobayashi, T., Kakeya, H., Miyazaki, T., Izumikawa, K., Yanagihara, K., Ohno, H., Yamamoto, Y., Tashiro, T., & Kohno, S.
- Affiliations
- Nagasaki University (JP)
- National Institute of Infectious Diseases (JP)
- ORCID
- Venue
- Japanese Journal of Infectious Diseases
- Publisher
- Editorial Committee of Japanese Journal of Infectious Diseases, National Institute of Infectious Dis
- Published
- 2011-07-29
- Volume
- 64
- Issue
- 4
- Pages
- 292-296
- ISSN
- 1344-6304 (ISSN-L)
- 1884-2836
- OpenAlex
- W4293117574
- Cited by
- 48
- References
- 1
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 4 · 2019: 4 · 2018: 2 · 2017: 6 · 2016: 5 · 2015: 3 · 2014: 2 · 2013: 3 · 2012: 2
- FWCI
- 1.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Japanese Journal of Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Health, Labour and Welfare
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- lactoferrin, azole antifungals, fluconazole, itraconazole, Candida albicans, invasive candidiasis, antifungal synergy, antifungal resistance, iron chelation, drug combination therapy
- MeSH terms
- Antifungal Agents, Candida albicans, Drug Combinations, Drug Synergism, Iron, Lactoferrin, Microbial Sensitivity Tests, Fluconazole, Itraconazole, Drug Resistance, Fungal, Candidiasis, Invasive
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