Genomics and Virulence ofFonsecaea pugnacius, Agent of Disseminated Chromoblastomycosis

Among agents of chromoblastomycosis,Fonsecaea pugnaciuspresents a unique type of infection because of its secondary neurotropic dissemination from a chronic cutaneous case in an immunocompetent patient. Neurotropism occurs with remarkable frequency in the fungal family Herpotrichiellaceae, possibly associated with the ability of some species to metabolize aromatic hydrocarbons. In an attempt to understand this new disease pattern, were conducted genomic analysis ofFonsecaea pugnacius(CBS 139214) performed withde novoassembly, gene prediction, annotation and mitochondrial genome assembly, supplemented with animal infection models performed withTenebrio molitorinMus musculuslineages BALB/c and C57BL/6. The genome draft of 34.8 Mb was assembled with a total of 12,217 protein-coding genes. Several proteins, enzymes and metabolic pathways related to extremotolerance and virulence were recognized. The enzyme profiles of black fungi involved in chromoblastomycosis and brain infection were analyzed with the Carbohydrate-Active Enzymes (CAZY) and peptidases database (MEROPS). The capacity of the fungus to survive insideTenebrio molitoranimal model was confirmed by histopathological analysis and by presence of melanin and hyphae in host tissue. AlthoughF. pugnaciuswas isolated from brain in a murine model following intraperitoneal infection, cytokine levels were not statistically significant, indicating a profile of an opportunistic agent. A dual ecological ability can be concluded from presence of metabolic pathways for nutrient scavenging and extremotolerance, combined with a capacity to infect human hosts.