Fluconazole-Resistant Candida auris Is Susceptible to Salivary Histatin 5 Killing and to Intrinsic Host Defenses.

is a newly identified species causing invasive candidemia and candidiasis. It has broad multidrug resistance (MDR) not observed for other pathogenic species. Histatin 5 (Hst 5) is a well-studied salivary cationic peptide with significant antifungal activity against and is an attractive candidate for treating MDR fungi, since antimicrobial peptides induce minimal drug resistance. We investigated the susceptibility of to Hst 5 and neutrophils, two first-line innate defenses in the human host. The majority of clinical isolates, including fluconazole-resistant strains, were highly sensitive to Hst 5: 55 to 90% of cells were killed by use of 7.5 μM Hst 5. Hst 5 was translocated to the cytosol and vacuole in cells; such translocation is required for the killing of by Hst 5. The inverse relationship between fluconazole resistance and Hst 5 killing suggests different cellular targets for Hst 5 than for fluconazole. showed higher tolerance to oxidative stress than , and higher survival within neutrophils, which correlated with resistance to oxidative stress Thus, resistance to reactive oxygen species (ROS) is likely one, though not the only, important factor in the killing of by neutrophils. Hst 5 has broad and potent candidacidal activity, enabling it to combat MDR strains effectively.