The Antifungal Activity of Lactoferrin and Its Derived Peptides Original paper
Researched by:
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Divine Aleru
ID
Divine Aleru
I am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
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Divine Aleru
Researched by:
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Divine Aleru
ID
Divine Aleru
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Divine Aleru
What was reviewed?
This review examined the antifungal properties of lactoferrin (Lf) and its derived peptides, especially lactoferricin, lactoferrampin, and Lf(1–11), highlighting their mechanisms of action and potential for synergistic use with antifungal drugs. The paper consolidated findings from multiple in vitro and some in vivo studies to explain how these molecules exert direct antifungal activity, modulate immune responses, and interact with current antifungal agents like azoles.
Who was reviewed?
The review synthesized studies involving a broad spectrum of fungal pathogens, particularly various Candida species, Cryptococcus, Aspergillus, and several plant-pathogenic molds. It also discussed work done on mammalian Lf peptides derived from human and bovine sources, tested on both wild-type and resistant fungal strains. Mechanistic and structural insights were drawn from both laboratory experiments and structural analyses of peptide variants.
What were the most important findings?
Lactoferrin and its derived peptides exhibit significant antifungal activity through membrane destabilization, iron chelation, and, in some cases, induction of fungal apoptosis-like processes. While initial assumptions attributed Lf’s antifungal effect to iron sequestration, more recent evidence points to direct membrane interaction and intracellular disruption as the primary mechanisms. These peptides quickly penetrate fungal cells, alter membrane potential, cause ROS accumulation, and trigger apoptosis pathways in C. albicans and S. cerevisiae.
Lf-derived peptides, especially bLfcin and Lfampin, show broad-spectrum activity at lower MICs than the full protein, and structural modifications enhance this potency. Synergy was most notable with azole-class drugs, where co-treatment reduced MICs for fluconazole and itraconazole-resistant Candida strains. For microbiome study, these findings are crucial: Lf and its peptides act selectively, impairing fungal overgrowth without broad-spectrum microbial destruction, preserving beneficial taxa, and possibly reinforcing mucosal barrier integrity through indirect immune modulation.
What are the implications of this review?
This review highlights lactoferrin’s therapeutic versatility, not only as a standalone antifungal agent but also as a synergistic enhancer of existing antifungal drugs. Its derived peptides, due to higher potency and customizable structures, represent promising leads for targeted antifungal drug design. For microbiome-informed clinical strategies, Lf peptides offer a selective approach to managing fungal overgrowth, reducing the risk of resistance development, and preserving microbial homeostasis. Their ability to weaken virulence traits (e.g., biofilm formation, hyphal growth) while enhancing host immune responses aligns well with personalized, microbiome-centered care pathways.