PDF(Pubmed)
Abstract：
Wound-invasive fungal diseases (WIFDs), especially mucormycosis, have emerged as life-threatening infections during recent military combat operations. Many combat-relevant fungal pathogens are refractory to current antifungal therapy. Therefore, animal models of WIFDs are urgently needed to investigate new therapeutic solutions. Our study establishes combat-relevant murine models of wound mucormycosis using Rhizopus arrhizus and Lichtheimia corymbifera, two Mucorales species that cause wound mucormycosis worldwide. These models recapitulate the characteristics of combat-related wounds from explosions, including blast overpressure exposure, full-thickness skin injury, fascial damage, and muscle crush. The independent inoculation of both pathogens caused sustained infections and enlarged wounds. Histopathological analysis confirmed the presence of necrosis and fungal hyphae in the wound bed and adjacent muscle tissue. Semi-quantification of fungal burden by colony-forming units corroborated the infection. Treatment with liposomal amphotericin B, 30 mg/kg, effectively controlled R. arrhizus growth and significantly reduced residual fungal burden in infected wounds (p < 0.001). This study establishes the first combat-relevant murine model of wound mucormycosis, paving the way for developing and evaluating novel antifungal therapies against combat-associated WIFDs.
摘要：
伤口侵袭性真菌病（WIFD），尤其是毛霉菌病,在最近的军事战斗行动中已经成为危及生命的感染。许多与战斗相关的真菌病原体对当前的抗真菌治疗是难以治疗的。因此,迫切需要WIFD的动物模型来研究新的治疗方案。我们的研究建立了使用根霉根霉和曲线菌的伤口毛霉菌病的战斗相关小鼠模型，在全世界引起伤口毛霉菌病的两种毛霉菌。这些模型概括了与战斗有关的爆炸伤口的特征，包括爆炸超压暴露，全层皮肤损伤，筋膜损伤,和肌肉挤压。两种病原体的独立接种导致持续感染和扩大的伤口。组织病理学分析证实伤口床和邻近肌肉组织中存在坏死和真菌菌丝。通过菌落形成单位对真菌负荷的半定量证实了感染。用脂质体两性霉素B治疗，30mg/kg,有效地控制了arrhizus的生长，并显着降低了感染伤口中残留的真菌负担（p<0.001）。本研究建立了第一个与战斗相关的小鼠伤口毛霉菌病模型，为开发和评估针对战斗相关WIFD的新型抗真菌疗法铺平了道路。
