Abstract
Eumycetoma is a chronic granulomatous subcutaneous infectious disease, endemic in tropical and subtropical regions and most commonly caused by the fungus Madurella mycetomatis. Interestingly, although grain formation is key in mycetoma, its formation process and its susceptibility towards antifungal agents are not well understood. This is because grain formation cannot be induced in vitro; a mammalian host is necessary to induce its formation. Until now, invertebrate hosts were never used to study grain formation in M. mycetomatis. In this study we determined if larvae of the greater wax moth Galleria mellonella could be used to induce grain formation when infected with M. mycetomatis. Three different M. mycetomatis strains were selected and three different inocula for each strain were used to infect G. mellonella larvae, ranging from 0.04 mg/larvae to 4 mg/larvae. Larvae were monitored for 10 days. It appeared that most larvae survived the lowest inoculum, but at the highest inoculum all larvae died within the 10 day observation period. At all inocula tested, grains were formed within 4 hours after infection. The grains produced in the larvae resembled those formed in human and in mammalian hosts. In conclusion, the M. mycetomatis grain model in G. mellonella larvae described here could serve as a useful model to study the grain formation and therapeutic responses towards antifungal agents in the future.
Highlights
Mycetoma is a chronic granulomatous subcutaneous infectious disease, characterized by massive deformities and disabilities
In this paper we describe the development of a Madurella mycetomatis grain model in Galleria mellonella larvae
We evaluated the survival of larvae when infected with different M. mycetomatis isolates and we verified the presence of grains in the tissue by histopathology
Summary
Mycetoma is a chronic granulomatous subcutaneous infectious disease, characterized by massive deformities and disabilities It is endemic in tropical and subtropical regions. A characteristic feature of mycetoma is the presence of grains inside the tissue These grains are formed by the micro-organisms upon entering the human body, probably as a defense mechanism against the human immune system [2]. Since so many different microorganisms are able to cause mycetoma, a large variety of grains can be formed These grains can be of different color, size, and consistency, depending on the causative micro-organism [2]. The grains of the most common causative agent M. mycetomatis are black, firm, and brittle and are 0.5–1 mm in size [3] They consist of densely packed fungal mycelia embedded in a hard and brown-black cement material. Surrounding the grain, an extensive granuloma formation is present, characterized by a large zone of neutrophils
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