Abstract
Fonsecaea and Cladophialophora are genera of black yeast-like fungi harboring agents of a mutilating implantation disease in humans, along with strictly environmental species. The current hypothesis suggests that those species reside in somewhat adverse microhabitats, and pathogenic siblings share virulence factors enabling survival in mammal tissue after coincidental inoculation driven by pathogenic adaptation. A comparative genomic analysis of environmental and pathogenic siblings of Fonsecaea and Cladophialophora was undertaken, including de novo assembly of F. erecta from plant material. The genome size of Fonsecaea species varied between 33.39 and 35.23 Mb, and the core genomes of those species comprises almost 70% of the genes. Expansions of protein domains such as glyoxalases and peptidases suggested ability for pathogenicity in clinical agents, while the use of nitrogen and degradation of phenolic compounds was enriched in environmental species. The similarity of carbohydrate-active vs. protein-degrading enzymes associated with the occurrence of virulence factors suggested a general tolerance to extreme conditions, which might explain the opportunistic tendency of Fonsecaea sibling species. Virulence was tested in the Galleria mellonella model and immunological assays were performed in order to support this hypothesis. Larvae infected by environmental F. erecta had a lower survival. Fungal macrophage murine co-culture showed that F. erecta induced high levels of TNF-α contributing to macrophage activation that could increase the ability to control intracellular fungal growth although hyphal death were not observed, suggesting a higher level of extremotolerance of environmental species.
Highlights
Melanized fungi belonging to the order Chaetothyriales are clinically relevant as agents of a gamut of diseases in humans and animals, varying in severity from superficial to systemic and fatal infections (De Hoog et al, 2004; Badali et al, 2008; Seyedmousavi et al, 2011)
The genus Fonsecaea is located in the Chaetothyriales, family Herpotrichiellaceae and contains species of environmental saprobes on plants or plant debris and pathogenic species, associated with subcutaneous and deep infections in human and animal hosts
The same phenomenon of environmental next to pathogenic species is known in Cladophialophora (Vicente et al, 2014)
Summary
Melanized fungi belonging to the order Chaetothyriales are clinically relevant as agents of a gamut of diseases in humans and animals, varying in severity from superficial to systemic and fatal infections (De Hoog et al, 2004; Badali et al, 2008; Seyedmousavi et al, 2011). Agents of chromoblastomycosis are traumatically inoculated from environmental sources such as plant thorns or wooden splinters carrying the respective opportunist (Salgado et al, 2004; De Hoog et al, 2007; Vicente et al, 2014). Those species are mainly found in Fonsecaea and Cladophialophora, of which F. pedrosoi, F. monophora, and Cladophialophora carrionii are recurrently recovered from patients in tropical and semi-arid climate zones, respectively around the globe (Xi et al, 2009; Queiroz-Telles, 2015). The genera Fonsecaea and Cladophialophora are morphologically classified by differences in their conidial apparatus; DNA polymorphisms suggest that both genera are polyphyletic (De Hoog et al, 2007), as they are distributed within “bantiana-clade” and “carrionii-clade” groups of the family Herpotrichiellaceae (Chaetothyriales) (Vicente et al, 2014; de Azevedo et al, 2015b)
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