Abstract

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 P. brasiliensis (Pb03 and Pb18) and one strain of P. lutzii. These genomes range in size from 28.8 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, suggesting that Onygenales, including dimorphic fungi, can decay simple plant biomass in the soil. By contrast, U. reesii showed extensive growth on a wide range of dipeptides and amino acids, indicating a ability to utilize proteinaceous growth substrates, and suggesting that these fungi can also degrade animal biomass. The ability to utilize a wide range of proteins coupled with the evolutionary conservation of protease diversity may have predisposed the dimorphic fungi, including Paracoccidioides, to a pathogenic lifestyle on a live animal host.