Protective Efficacy of Anti-Hyr1p Monoclonal Antibody against Systemic Candidiasis Due to Multi-Drug-Resistant Candida auris.
Protective Efficacy of Anti-Hyr1p Monoclonal Antibody against Systemic Candidiasis Due to Multi-Drug-Resistant Candida auris.
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DOI：
10.3390/jof9010103
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发表时间：
2023-01-12
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--
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耳念珠菌是一种多重耐药真菌病原体，可以在宿主外存活，并且可以很容易地传播和定殖医疗保健环境，医疗器械和人体皮肤。C.耳炎会导致住在这种受污染的卫生保健设施中的免疫抑制患者的严重危及生命的感染（高达60%的死亡率）。C.耳对几乎所有临床上可用的抗真菌药物都有抗性。因此，迫切需要替代治疗方法。使用计算机蛋白质建模和分析，我们确定了一个高度免疫原性和表面暴露的表位，是保守的C。白念珠菌菌丝调节蛋白（Cal-Hyr 1 p）和Hyr 1 p/Iff样蛋白在白念珠菌中的表达。auris（Cau-HILp）。我们生成了针对该Cal-Hyr 1 p表位的单克隆抗体（MAb），该抗体识别几种临床分离的C.代表所有四个分支的耳。抗Hyr 1 p单克隆抗体阻止生物膜形成并增强调理吞噬细胞对C.巨噬细胞的作用。当进行体内效力测试时，抗Hyr 1 p单克隆抗体保护55%的小鼠免受致死性系统性C。耳感染，并表现出显着减少真菌负担。我们的研究具有高度临床相关性，并为治疗MDR C引起的感染提供了有效的替代治疗选择。耳。
Candida auris is a multi-drug-resistant fungal pathogen that can survive outside the host and can easily spread and colonize the healthcare environment, medical devices, and human skin. C. auris causes serious life-threatening infections (up to 60% mortality) in immunosuppressed patients staying in such contaminated healthcare facilities. Some isolates of C. auris are resistant to virtually all clinically available antifungal drugs. Therefore, alternative therapeutic approaches are urgently needed. Using in silico protein modeling and analysis, we identified a highly immunogenic and surface-exposed epitope that is conserved between C. albicans hyphal-regulated protein (Cal-Hyr1p) and Hyr1p/Iff-like proteins in C. auris (Cau-HILp). We generated monoclonal antibodies (MAb) against this Cal-Hyr1p epitope, which recognized several clinical isolates of C. auris representing all four clades. An anti-Hyr1p MAb prevented biofilm formation and enhanced opsonophagocytic killing of C. auris by macrophages. When tested for in vivo efficacy, anti-Hyr1p MAb protected 55% of mice against lethal systemic C. auris infection and showed significantly less fungal burden. Our study is highly clinically relevant and provides an effective alternative therapeutic option to treat infections due to MDR C. auris.
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