AUTHOR=Vicente Vania A. , Weiss Vinícius A. , Bombassaro Amanda , Moreno Leandro F. , Costa Flávia F. , Raittz Roberto T. , Leão Aniele C. , Gomes Renata R. , Bocca Anamelia L. , Fornari Gheniffer , de Castro Raffael J. A. , Sun Jiufeng , Faoro Helisson , Tadra-Sfeir Michelle Z. , Baura Valter , Balsanelli Eduardo , Almeida Sandro R. , Dos Santos Suelen S. , Teixeira Marcus de Melo , Soares Felipe Maria S. , do Nascimento Mariana Machado Fidelis , Pedrosa Fabio O. , Steffens Maria B. , Attili-Angelis Derlene , Najafzadeh Mohammad J. , Queiroz-Telles Flávio , Souza Emanuel M. , De Hoog Sybren 

TITLE=Comparative Genomics of Sibling Species of Fonsecaea Associated with Human Chromoblastomycosis

JOURNAL=Frontiers in Microbiology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.01924

DOI=10.3389/fmicb.2017.01924

ISSN=1664-302X

ABSTRACT=<p><italic>Fonsecaea</italic> and <italic>Cladophialophora</italic> 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 <italic>Fonsecaea</italic> and <italic>Cladophialophora</italic> was undertaken, including <italic>de novo</italic> assembly of <italic>F. erecta</italic> from plant material. The genome size of <italic>Fonsecaea</italic> 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 <italic>Fonsecaea</italic> sibling species. Virulence was tested in the <italic>Galleria mellonella</italic> model and immunological assays were performed in order to support this hypothesis. Larvae infected by environmental <italic>F. erecta</italic> had a lower survival. Fungal macrophage murine co-culture showed that <italic>F. erecta</italic> 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.</p>