Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, MD, USA.
FEBS Open Bio. 2021 Oct;11(10):2727-2739. doi: 10.1002/2211-5463.13271. Epub 2021 Sep 9.
Mycoplasma hyorhinis (M. hyorhinis) lacks a cell wall and resists multiple antibiotics. We describe here the striking > 90% inhibitory effect of hemin, a natural inducer of the cytoprotective enzyme heme oxygenase-1 (HO-1), on M. hyorhinis replication in chronically infected LNCaP prostate cancer cells. The role of HO-1 in interrupting M. hyorhinis replication was confirmed by HO-1-specific siRNA suppression of hemin-induced HO-1 protein expression, which increased intracellular M. hyorhinis DNA levels in LNCaP cells. Proteomic analysis and transmission electron microscopy of hemin-treated cells confirmed the complete absence of M. hyorhinis proteins and intact microorganisms, respectively, strongly supporting these findings. Our study is the first to our knowledge suggesting therapeutic potential for activated HO-1 in cellular innate responses against mycoplasma infection.
猪鼻支原体（M. hyorhinis）缺乏细胞壁，并且对多种抗生素具有耐药性。我们在此描述了血红素（一种天然诱导细胞保护酶血红素加氧酶-1（HO-1）的物质）对慢性感染 LNCaP 前列腺癌细胞中 M. hyorhinis 复制的惊人> 90%的抑制作用。HO-1 在中断 M. hyorhinis 复制中的作用通过 HO-1 特异性 siRNA 抑制血红素诱导的 HO-1 蛋白表达得到证实，这增加了 LNCaP 细胞中细胞内 M. hyorhinis DNA 水平。血红素处理细胞的蛋白质组学分析和透射电子显微镜分别证实了支原体蛋白的完全缺失和完整微生物的存在，这强有力地支持了这些发现。我们的研究首次表明，激活的 HO-1 在细胞固有反应中对抗支原体感染具有治疗潜力。
