title: Comparative genomic analysis of human fungal pathogens causing paracoccidioidomycosis.
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 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.
authors: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors: Christopher A
authors: CA
authors: Desjardins
authors: Mia D
authors: MD
authors: Champion
authors: Jason W
authors: JW
authors: Holder
authors: Anna
authors: A
authors: Muszewska
authors: Jonathan
authors: J
authors: Goldberg
authors: Alexandre M
authors: AM
authors: Bailão
authors: Marcelo Macedo
authors: MM
authors: Brigido
authors: Márcia Eliana da Silva
authors: ME
authors: Ferreira
authors: Ana Maria
authors: AM
authors: Garcia
authors: Marcin
authors: M
authors: Grynberg
authors: Sharvari
authors: S
authors: Gujja
authors: David I
authors: DI
authors: Heiman
authors: Matthew R
authors: MR
authors: Henn
authors: Chinnappa D
authors: CD
authors: Kodira
authors: Henry
authors: H
authors: León-Narváez
authors: Larissa V G
authors: LV
authors: Longo
authors: Li-Jun
authors: LJ
authors: Ma
authors: Iran
authors: I
authors: Malavazi
authors: Alisson L
authors: AL
authors: Matsuo
authors: Flavia V
authors: FV
authors: Morais
authors: Maristela
authors: M
authors: Pereira
authors: Sabrina
authors: S
authors: Rodríguez-Brito
authors: Sharadha
authors: S
authors: Sakthikumar
authors: Silvia M
authors: SM
authors: Salem-Izacc
authors: Sean M
authors: SM
authors: Sykes
authors: Marcus Melo
authors: MM
authors: Teixeira
authors: Milene C
authors: MC
authors: Vallejo
authors: Maria Emília Machado Telles
authors: ME
authors: Walter
authors: Chandri
authors: C
authors: Yandava
authors: Sarah
authors: S
authors: Young
authors: Qiandong
authors: Q
authors: Zeng
authors: Jeremy
authors: J
authors: Zucker
authors: Maria Sueli
authors: MS
authors: Felipe
authors: Gustavo H
authors: GH
authors: Goldman
authors: Brian J
authors: BJ
authors: Haas
authors: Juan G
authors: JG
authors: McEwen
authors: Gustavo
authors: G
authors: Nino-Vega
authors: Rosana
authors: R
authors: Puccia
authors: Gioconda
authors: G
authors: San-Blas
authors: Celia Maria de Almeida
authors: CM
authors: Soares
authors: Bruce W
authors: BW
authors: Birren
authors: Christina A
authors: CA
authors: Cuomo
mesh_terms: D050260:Carbohydrate Metabolism / Q000235:genetics; D016503:Drug Delivery Systems; D019143:Evolution, Molecular; D016681:Genome, Fungal; D054629:Genome, Mitochondrial / Q000235:genetics; D006801:Humans; D005810:Multigene Family / Q000235:genetics; D020036:Onygenales / Q000201:enzymology / Q000235:genetics*; D010228:Paracoccidioides / Q000201:enzymology / Q000235:genetics*; D010229:Paracoccidioidomycosis / Q000382:microbiology*; D010802:Phylogeny; D011494:Protein Kinases / Q000235:genetics*; D059748:Proteolysis; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D011494:Protein Kinases