A New Murine Model of Cutaneous Aspergillosis in a Large Skin Defect

A. M. Tatara1 , N. D. Albert2 , A. G. Mikos1 , D. P. Kontoyiannis2

Author address: 

1Rice Univ., Houston, TX, 2The Univ. of Texas MD Anderson Cancer, Houston, TX


Background: Cutaneous aspergillosis is a clinically challenging condition to resolve. In part, this is due to the ability of Aspergillus to invade local blood vessels and suppress host angiogenesis, resulting in large necrotic ulcers with poor innate regenerative capacity[1]. In order to better understand this disease process, as well as build a platform for developing improved therapeutic strategies, we have created a new murine model of cutaneous aspergillosis featuring a large skin defect.Methods: Chemically immunosuppressed BALB/c mice[1] were inoculated with subcutaneous injections of either saline or 1.75x106 conidia/mL A. fumigatus Af293. After 72 hours, a full-thickness surgical wound of 5mm was created with a sterile biopsy punch and the wound was re-inoculated at the same dosage. Every 3 days, the size of the wound bed was measured. Mice were euthanized at Day 9 (n=5 per group, performed in duplicate) and Day 18 (n=5 per group). After euthanasia, the wound bed was harvested subjected to histologic analysis for host inflammation and presence of fungi.Results: As early as day 9, the rate of cutaneous wound healing was significantly inhibited by the presence of Aspergillus infection (wound area reduction of 13.5%, p=0.55), whereas saline groups demonstrated significant reduction of wound area (39.0%, p=0.017). Viable A. fumigatus could still be recovered from the wound bed at least two weeks after the initial infection. Histology revealed the presence of hyphae and inflammation in infected wound beds at time of euthanasia.Conclusions: We have successfully created a murine model of chronic cutaneous aspergillosis infection of a large tissue defect with impaired wound healing. This model reproducibly recapitulates the impaired wound healing seen in immunocompromised patients. Unlike previous work, this model allows for 1) real-time macroscopic assessment of healing of a large cutaneous Aspergillus-infected wound, 2) chronicity of infection, and 3) the ability to test novel local therapies for fungal-infected wound beds in the future.

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Full conference title: 

ASM Microbe 2016
    • ASM microbe 1st (2016)