Seifi Zahra, Shokohi Tahereh, Shafiee Mohammad, Mowla Seyed Javad, Niknejad Farhad, Siddig Emmanuel Edwar, Ahmed Ayman, Abastabar Mahdi, Vahedi Larijani Laleh
Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran.
Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
Microbiol Spectr. 2025 Jul;13(7):e0285224. doi: 10.1128/spectrum.02852-24. Epub 2025 Jun 9.
The spore coat protein homolog (CotH) has been identified among virulence factors of Mucorales that mediate fungal invasion by glucose-regulated protein 78 (GRP78) ligand on endothelial cells. The aim of this study was to examine the gene expressions of spore coat protein homolog 3 (CotH3) and GRP78, along with their target miRNAs, in infected human macrophages, mice models, and mucormycosis patients. To assess changes in the relative expressions of the GPR78 and CotH3 genes, this study used the real-time quantitative PCR method to quantify their target miRNAs in macrophages derived from human monocytes (monocyte-derived macrophages [MDMs]), mice models, and sinus tissue from diabetic patients with mucormycosis. In this study, expressions of GRP78 and CotH3 genes were elevated in infected MDMs and non-diabetic Balb/c mice infected with , and the expression of the GRP78 gene was upregulated in the non-infected diabetic mice. However, the infected diabetic mice displayed a decline in the GRP78 gene expression. Moreover, although the expression of the GRP78 gene increased in the sinus tissue of diabetic patients with mucormycosis, it significantly decreased in the same patients after treatment. The relative expression of hsa-miR-16-5p, hsa-miR-93-3p, and hsa-miR-335-5p was downregulated in the MDMs. The increased gene expression levels of CotH3 and GPR78 observed in infected macrophages provide insight into the mechanism of interactions between the pathogen and macrophages. Prolonged encounters lead to changes in the expression levels of CotH3 and GPR78 genes.
The research delves into the intricate gene expression patterns of CotH3, a homolog of CotH, and GRP78 in human macrophages, mice models, and diabetic patients afflicted with mucormycosis. The study's findings underscore the pivotal role of diabetes in the host-pathogen interaction, revealing that diabetic conditions amplify the expression of the GRP78 gene, thereby escalating the risk of fungal invasion and growth. This research paper is crucial as it sheds light on the intricate mechanisms underlying mucormycosis infection and underscores the heightened vulnerability of diabetic individuals. By elucidating the roles of CotH3 and GRP78 in the infection process, the study contributes to a deeper understanding of mucormycosis pathogenesis and paves the way for the development of targeted therapeutic strategies.
在毛霉目真菌的毒力因子中已鉴定出孢子壁蛋白同源物（CotH），其通过内皮细胞上的葡萄糖调节蛋白78（GRP78）配体介导真菌侵袭。本研究的目的是检测感染的人类巨噬细胞、小鼠模型和毛霉菌病患者中孢子壁蛋白同源物3（CotH3）和GRP78及其靶miRNA的基因表达。为了评估GPR78和CotH3基因相对表达的变化，本研究采用实时定量PCR方法对来自人类单核细胞的巨噬细胞（单核细胞衍生的巨噬细胞[MDM]）、小鼠模型和糖尿病毛霉菌病患者鼻窦组织中的靶miRNA进行定量。在本研究中，GRP78和CotH3基因在感染的MDM和感染的非糖尿病Balb/c小鼠中表达升高，GRP78基因在未感染的糖尿病小鼠中表达上调。然而，感染的糖尿病小鼠GRP78基因表达下降。此外，虽然糖尿病毛霉菌病患者鼻窦组织中GRP78基因表达增加，但治疗后同一患者该基因表达显著下降。hsa-miR-16-5p、hsa-miR-93-3p和hsa-miR-335-5p在MDM中的相对表达下调。在感染的巨噬细胞中观察到的CotH3和GPR78基因表达水平升高，为病原体与巨噬细胞之间的相互作用机制提供了见解。长时间接触导致CotH3和GPR78基因表达水平发生变化。
该研究深入探讨了CotH的同源物CotH3和GRP78在人类巨噬细胞、小鼠模型和患有毛霉菌病的糖尿病患者中的复杂基因表达模式。该研究结果强调了糖尿病在宿主-病原体相互作用中的关键作用，表明糖尿病状态会放大GRP78基因的表达，从而增加真菌侵袭和生长的风险。这篇研究论文至关重要，因为它揭示了毛霉菌病感染的复杂机制，并强调了糖尿病个体更高易感性。通过阐明CotH3和GRP78在感染过程中的作用，该研究有助于更深入地理解毛霉菌病发病机制，并为开发靶向治疗策略铺平道路。
