Comparative genomic analysis of human fungal pathogens causing paracoccidioidomycosis
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2011
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Paracoccidioides is a fungal pathogen and the cause of paracoccidioidomycosis, a health-threatening human systemic
mycosis endemic to Latin America. Infection by Paracoccidioides, a dimorphic fungus in the order Onygenales, is coupled
with a thermally regulated transition from a soil-dwelling filamentous form to a yeast-like pathogenic form. To better
understand the genetic basis of growth and pathogenicity in Paracoccidioides, we sequenced the genomes of two strains of
Paracoccidioides brasiliensis (Pb03 and Pb18) and one strain of Paracoccidioides lutzii (Pb01). These genomes range in size
from 29.1 Mb to 32.9 Mb and encode 7,610 to 8,130 genes. To enable genetic studies, we mapped 94% of the P. brasiliensis
Pb18 assembly onto five chromosomes. We characterized gene family content across Onygenales and related fungi, and
within Paracoccidioides we found expansions of the fungal-specific kinase family FunK1. Additionally, the Onygenales have
lost many genes involved in carbohydrate metabolism and fewer genes involved in protein metabolism, resulting in a
higher ratio of proteases to carbohydrate active enzymes in the Onygenales than their relatives. To determine if gene
content correlated with growth on different substrates, we screened the non-pathogenic onygenale Uncinocarpus reesii,
which has orthologs for 91% of Paracoccidioides metabolic genes, for growth on 190 carbon sources. U. reesii showed
growth on a limited range of carbohydrates, primarily basic plant sugars and cell wall components; this suggests that
Onygenales, including dimorphic fungi, can degrade cellulosic plant material in the soil. In addition, U. reesii grew on gelatin
and a wide range of dipeptides and amino acids, indicating a preference for proteinaceous growth substrates over
carbohydrates, which may enable these fungi to also degrade animal biomass. These capabilities for degrading plant and
animal substrates suggest a duality in lifestyle that could enable pathogenic species of Onygenales to transfer from soil to
animal hosts.
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DESJARDINS, Christopher A. et al. Comparative genomic analysis of human fungal pathogens causing paracoccidioidomycosis. PLOS Genetics, San Francisco, v. 7, n. 10, e1002345, 2011.