Comparative genomic analysis of human fungal pathogens causing paracoccidioidomycosis.
Сравнительное исследованиеСтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Desjardins Christopher A, Champion Mia D, Holder Jason W, Muszewska Anna, Goldberg Jonathan, Bailão Alexandre M, Brigido Marcelo Macedo, Ferreira Márcia Eliana da Silva, Garcia Ana Maria, Grynberg Marcin, Gujja Sharvari, Heiman David I, Henn Matthew R, Kodira Chinnappa D, León-Narváez Henry, Longo Larissa V G, Ma Li-Jun, Malavazi Iran, Matsuo Alisson L, Morais Flavia V, Pereira Maristela, Rodríguez-Brito Sabrina, Sakthikumar Sharadha, Salem-Izacc Silvia M, Sykes Sean M, Teixeira Marcus Melo, Vallejo Milene C, Walter Maria Emília Machado Telles, Yandava Chandri, Young Sarah, Zeng Qiandong, Zucker Jeremy, Felipe Maria Sueli, Goldman Gustavo H, Haas Brian J, McEwen Juan G, Nino-Vega Gustavo, Puccia Rosana, San-Blas Gioconda, Soares Celia Maria de Almeida, Birren Bruce W, Cuomo Christina A
Аннотация
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.