Antifungal activity of the antimicrobial peptide RP557 against priority fungal pathogens

<b>Background.</b> Natural host defence molecules, part of innate immunity and the first line of defence, are evolutionarily conserved. Some pharmaceutical properties undesirable for clinical use led to the rational design of synthetic molecules with constructed peptide arrangements, giving a novel therapeutic avenue. A prior publication showed synthetic peptide RP557 inhibition and killing of fluconazole-sensitive and resistant <i>Candida</i> species isolates, biofilm inhibition, no resistance induction, direct membrane action, negligible mammalian cell toxicity and topical efficacy in a rodent vaginal candidiasis model. These findings highlight the relevance of investigating RP557 activity against other fungal pathogens.<b>Objective.</b> We evaluated the antifungal spectrum of the RP557 against World Health Organization-listed priority fungal pathogens, including endemic and skin fungal pathogens, both alone and in combination with commercial antifungal drugs.<b>Methods.</b> The antifungal spectrum was evaluated by broth dilution vs. clinical isolates, and we present 76 MICs (mcg ml^-1) performed according to M27 or M38 CLSI documents, 35 checkerboard interactions with antifungals and 10 minimum fungicidal determinations.<b>Results.</b> Overall impression is robust activity vs. chromoblastomycosis and mycetoma species, <i>Cryptococcus neoformans</i> and <i>Trichophyton</i> spp.; broad MIC ranges within most species, least activity vs. <i>Mucorales</i> and <i>Aspergillus</i> spp.; and some promising drug interactions vs. <i>Sporothrix</i> spp. and <i>Candida auris</i>.<b>Conclusion.</b> Additional efficacy data <i>in vivo</i> is needed. Topical therapy could give local concentrations exceeding MICs, and burn or trauma prophylaxis or treatments are attractive potential targets owing to RP557 panmicrobial properties.