Department of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, New York, USA.
Department of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, New York, USA
Antimicrob Agents Chemother. 2018 Jan 25;62(2). doi: 10.1128/AAC.01872-17. Print 2018 Feb.
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.
是一种新鉴定的物种，可引起侵袭性念珠菌血症和念珠菌病。它具有广泛的多药耐药性（MDR），这在其他致病物种中未观察到。组蛋白 5（Hst 5）是一种研究充分的唾液阳离子肽，对具有显著的抗真菌活性，并且是治疗多药耐药真菌的有吸引力的候选物，因为抗菌肽诱导的耐药性最小。我们研究了 Hst 5 和中性粒细胞对的易感性，这是宿主中两种一线先天防御。大多数临床分离株，包括氟康唑耐药株，对 Hst 5 高度敏感：使用 7.5 μM Hst 5 可杀死 55%至 90%的细胞。Hst 5 被转运到细胞溶胶和中；这种转运对于 Hst 5 杀死是必需的。氟康唑耐药性与 Hst 5 杀伤之间的反比关系表明，Hst 5 的细胞靶标与氟康唑不同。与相比，对氧化应激的耐受性更高，并且在中性粒细胞内的存活率更高，这与对氧化应激的抗性相关。因此，对活性氧（ROS）的耐药性可能是中性粒细胞杀伤的一个重要因素（尽管不是唯一因素）。Hst 5 具有广泛而有效的杀真菌活性，能够有效对抗 MDR 菌株。
