Lactoferrin is broadly active against yeasts and highly synergistic with amphotericin B.

PMID: 

Antimicrob Agents Chemother. 2020 Feb 24. Epub 2020 Feb 24. PMID: 32094132

Abstract Title: 

Lactoferrin is broadly active against yeasts and highly synergistic with amphotericin B.

Abstract: 

Lactoferrin (LF) is a multifunctional milk protein with antimicrobial activity against a range of pathogens. While numerous studies report that LF is active against fungi, there are considerable differences in the level of antifungal activity and the capacity of LF to interact with other drugs. Here we undertake a comprehensive evaluation of the antifungal spectrum of activity of three defined sources of LF across 22 yeast and 24 mould species, and assess interactions with six widely used antifungal drugs. LF was broadly and consistently active across all yeast species (MIC 8-64μg/ml), with the extent of activity strongly affected by iron saturation. LF was synergistic with amphotericin B (AMB) in 19 out of 22 yeast species tested and synergy was unaffected by iron saturation but affected by the extent of LF digestion. LF+AMB combination therapy significantly prolonged the survival ofinfected withorand decreased fungal burden 12-25 fold. Evidence that LF directly interacts with the fungal cell surface was seen via SEM, which showed pore formation, hyphal thinning and major cell collapse in response to LF+AMB synergy. Important virulence mechanisms were disrupted by LF+AMB treatment, which significantly prevented biofilms inandinhibited hyphal development in, and reduced cell and capsule size and phenotypic diversity inOur results demonstrate the potential of LF+AMB as an antifungal treatment that is broadly synergistic against important yeast pathogens, with synergy attributed to the presence of one or more LF peptides.

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