A Model for Trans-Kingdom Pathogenicity in Fonsecaea Agents of Human Chromoblastomycosis

Abstract

The fungal genus Fonsecaea comprises etiological agents of human chromoblastomycosis, a chronic implantation skin disease. The current hypothesis is that patients acquire the infection through an injury from plant material. The present study aimed to evaluate a model of infection in plant and animal hosts to understand the parameters of trans-kingdom pathogenicity. Clinical strains of causative agents of chromoblastomycosis (Fonsecaea pedrosoi and Fonsecaea monophora) were compared with a strain of Fonsecaea erecta isolated from a living plant. The clinical strains of F. monophora and F. pedrosoi remained concentrated near the epidermis, whereas F. erecta colonized deeper plant tissues, resembling an endophytic behavior. In an invertebrate infection model with larvae of a beetle, Tenebrio molitor, F. erecta exhibited the lowest survival rates. However, F. pedrosoi produced dark, spherical to ovoidal cells that resembled muriform cells, the invasive form of human chromoblastomycosis confirming the role of muriform cells as a pathogenic adaptation in animal tissues. An immunologic assay in BALB/c mice demonstrated the high virulence of saprobic species in animal models was subsequently controlled via host higher immune response.

Genomics and Virulence of Fonsecaea pugnacius, Agent of Disseminated Chromoblastomycosis

“…After 24 h, the larvae infected with F. pugnacius presented a dark pigmentation, caused by melanization in the hemolymph, which was observed during the entire 10-day period of analysis by visual observation and spectrophotometry ( Figure 4C). Similar results were obtained by Fornari et al (2018) in Fonsecaea siblings, showing maximum melanization with 24 h post infection. The capacity of the fungus to survive inside the larvae was confirmed by histopathology, revealing melanized hyphae in tissue that had developed within 4-72 h ( Figure 4D).…”

“…The larvae infected with F. pugnacius exhibited higher mortality rates than control groups, PBS and SHAM ( Figure 4A). Fonsecaea pugnacius presented a lower mortality rate than F. monophora, F. erecta, and F. pedrosoi, as reported by Fornari et al (2018). This indicates that F. pugnacius infection presents a slower development compared to Fonsecaea siblings involved in chromoblastomycosis, as well as to environmental saprobes.…”

“…A Tenebrio molitor larval model was used to evaluate the virulence potential based on Fornari et al (2018) using parameters of survival and melanization after infection. Larvae were inoculated with 1 × 10 6 cells/mL in PBS solution above the legs and the ventral portion sterile PBS solution and SHAM without physical damage (no treatment) as negative control, using 10 larvae per group of inoculation, in triplicate.…”

Molecular characterization of siderophore biosynthesis in Paracoccidioides brasiliensis

“…An alternative that has been explored are larvae of T. molitor , an animal that is easy to handle, is marketed by several suppliers and is a low cost insect. Furthermore, the T. molitor larvae have been standardized as an in vivo infection model for several fungal pathogens as C. albicans , C. neoformans , Malassezia furfur and Fonsecaea pedrosoi (de Souza et al 2015 ; Silva et al 2018 ; Fornari et al 2018 ). Here, we explored the application of T. molitor as an invertebrate infection model for P. brasiliensis .…”

Environmental prospecting of black yeast-like agents of human disease using culture-independent methodology

“…In our study, the non-pathogenic Fonsecaea species were not detected. A study presented an in vitro plant infection model showing that the agents of human chromoblastomycosis have a certain degree of plant-invasive ability 30 , suggesting that those species occur on plants as well. We may hypothesize, that both strictly saprobic and opportunistic species are very rare and thus both have a low chance to be detected in non-optimal datasets using unbiased methodology.…”