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Development of a Combat-Relevant Murine Model of Wound Mucormycosis: A Platform for the Pre-Clinical Investigation of Novel Therapeutics for Wound-Invasive Fungal Diseases.
Samdavid Thanapaul, Rex J R; Alamneh, Yonas A; Finnegan, Daniel K; Antonic, Vlado; Abu-Taleb, Rania; Czintos, Christine; Boone, Dylan; Su, Wanwen; Sajja, Venkatasivasai S; Getnet, Derese; Roberds, Ashleigh; Walsh, Thomas J; Bobrov, Alexander G.
  • Samdavid Thanapaul RJR; Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Alamneh YA; NRC Research Associateship Programs, National Academies of Sciences, Engineering, and Medicine, Washington, DC 20001, USA.
  • Finnegan DK; Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Antonic V; Veterinary Services Program, Pathology Department, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Abu-Taleb R; Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Czintos C; Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Boone D; Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Su W; Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Sajja VS; Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Getnet D; Blast Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Roberds A; Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Walsh TJ; Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Bobrov AG; Departments of Medicine and Microbiology & Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
J Fungi (Basel) ; 10(5)2024 May 20.
Article en En | MEDLINE | ID: mdl-38786719
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.
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