The Emerging Pathogen Candida auris: Growth Phenotype, Virulence Factors, Activity of Antifungals, and Effect of SCY-078, a Novel Glucan Synthesis Inhibitor, on Growth Morphology and Biofilm Formation.
The Emerging Pathogen Candida auris: Growth Phenotype, Virulence Factors, Activity of Antifungals, and Effect of SCY-078, a Novel Glucan Synthesis Inhibitor, on Growth Morphology and Biofilm Formation.
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DOI：
10.1128/aac.02396-16
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发表时间：
2017-05
影响因子：
4.9
通讯作者：
Ghannoum M
中科院分区：
文献类型：
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作者：
Larkin E;Hager C;Chandra J;Mukherjee PK;Retuerto M;Salem I;Long L;Isham N;Kovanda L;Borroto-Esoda K;Wring S;Angulo D;Ghannoum M
耳念珠菌，一种新的多重耐药念珠菌属。最近出现了一种与侵袭性感染和高死亡率相关的疾病。在这里，我们确定了 16 种耳念珠菌分离株的毒力因子（发芽、粘附、生物膜形成、磷脂酶和蛋白酶产生）及其对属于不同抗真菌类别的 11 种药物的敏感性，包括一种新型口服生物可利用的 1,3-β-d-葡聚糖合成抑制剂 (SCY-078)。我们还研究了 SCY-078 对耳念珠菌生长、超微结构和生物膜形成能力的影响。我们的数据显示，虽然测试菌株没有发芽，但它们确实以菌株依赖性方式产生磷脂酶和蛋白酶，并且与白色念珠菌相比，粘附和形成生物膜的能力显着降低（P = 0.01）。耳念珠菌分离株对氟康唑和两性霉素 B 的敏感性降低，而一般来说，它们对其余测试药物敏感。 SCY-078 对耳念珠菌的 MIC90 为 1 mg/L，并且完全抑制耳念珠菌和白色念珠菌的生长。扫描电子显微镜分析表明，SCY-078 中断耳念珠菌细胞分裂，使该生物体形成异常的融合真菌细胞。此外，SCY-078 具有有效的抗生物膜活性，其中与未处理的对照相比，经处理的生物膜表现出显着降低的代谢活性和显着降低的厚度（两次比较 P < 0.05）。我们的研究表明，耳念珠菌表达几种毒力决定因素（尽管程度低于白色念珠菌），并且对氟康唑和两性霉素 B 具有耐药性。SCY-078（一种新型口服生物可利用的抗真菌药）对耳念珠菌具有有效的抗真菌/抗生物膜活性，表明有必要进一步评估这种抗真菌药物。
Candida auris, a new multidrug-resistant Candida spp. which is associated with invasive infection and high rates of mortality, has recently emerged. Here, we determined the virulence factors (germination, adherence, biofilm formation, phospholipase and proteinase production) of 16 C. auris isolates and their susceptibilities to 11 drugs belonging to different antifungal classes, including a novel orally bioavailable 1,3-β-d-glucan synthesis inhibitor (SCY-078). We also examined the effect of SCY-078 on the growth, ultrastructure, and biofilm-forming abilities of C. auris. Our data showed that while the tested strains did not germinate, they did produce phospholipase and proteinase in a strain-dependent manner and had a significantly reduced ability to adhere and form biofilms compared to that of Candida albicans (P = 0.01). C. auris isolates demonstrated reduced susceptibility to fluconazole and amphotericin B, while, in general, they were susceptible to the remaining drugs tested. SCY-078 had an MIC90 of 1 mg/liter against C. auris and caused complete inhibition of the growth of C. auris and C. albicans. Scanning electron microscopy analysis showed that SCY-078 interrupted C. auris cell division, with the organism forming abnormal fused fungal cells. Additionally, SCY-078 possessed potent antibiofilm activity, wherein treated biofilms demonstrated significantly reduced metabolic activity and a significantly reduced thickness compared to the untreated control (P < 0.05 for both comparisons). Our study shows that C. auris expresses several virulence determinants (albeit to a lesser extent than C. albicans) and is resistant to fluconazole and amphotericin B. SCY-078, the new orally bioavailable antifungal, had potent antifungal/antibiofilm activity against C. auris, indicating that further evaluation of this antifungal is warranted.