Rhizopus arrhizus infection induces histopathological lung injury and alters immune and membrane-associated pathways in a murine model

Abstract

As a major pathogenic fungus of the Rhizopodaceae family, Rhizopus arrhizus can infect humans and lead to severe outcomes, including life-threatening systemic infections. In this study, a fungal strain designated XML01 was isolated from a goat specimen. Following cultivation on potato dextrose agar (PDA), the isolate was identified as Rhizopus arrhizus through lactophenol cotton blue staining, scanning electron microscopy, and ITS gene sequencing. To investigate the pulmonary pathogenicity and mechanistic underpinnings of this strain, a murine model was established and analyzed using histopathological techniques (HE and Gomori's methenamine silver staining), RT-qPCR, and transcriptome sequencing. Infection with R. arrhizus resulted in significant pulmonary damage, characterized by alveolar wall thickening, severe hemorrhage, inflammatory cell infiltration, and interstitial hyperplasia. Transcriptome analysis revealed 318 significantly differentially expressed genes, predominantly enriched in pathways related to ciliary motility, cGMP-PKG signaling, and calcium homeostasis—indicating profound disruption of normal lung function. Key downregulated genes were associated with the IL-17 and B-cell receptor signaling pathways. Notably, SftpC and GSN were significantly upregulated, while Fth1, Scgb3a1, and Scgb1a1 were downregulated, findings that were consistent with RT-qPCR validation. Collectively, this work provides a novel and highly reproducible animal model that deepens the understanding of pathogenesis and offers a valuable tool for the development of new therapies for mucormycosis.