Dataset Information

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.

SUBMITTER: Desjardins CA

PROVIDER: S-EPMC3203195 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Comparative genomic analysis of human fungal pathogens causing paracoccidioidomycosis.

Desjardins Christopher A CA Champion Mia D MD Holder Jason W JW Muszewska Anna A Goldberg Jonathan J Bailão Alexandre M AM Brigido Marcelo Macedo MM Ferreira Márcia Eliana da Silva ME Garcia Ana Maria AM Grynberg Marcin M Gujja Sharvari S Heiman David I DI Henn Matthew R MR Kodira Chinnappa D CD León-Narváez Henry H Longo Larissa V G LV Ma Li-Jun LJ Malavazi Iran I Matsuo Alisson L AL Morais Flavia V FV Pereira Maristela M Rodríguez-Brito Sabrina S Sakthikumar Sharadha S Salem-Izacc Silvia M SM Sykes Sean M SM Teixeira Marcus Melo MM Vallejo Milene C MC Walter Maria Emília Machado Telles ME Yandava Chandri C Young Sarah S Zeng Qiandong Q Zucker Jeremy J Felipe Maria Sueli MS Goldman Gustavo H GH Haas Brian J BJ McEwen Juan G JG Nino-Vega Gustavo G Puccia Rosana R San-Blas Gioconda G Soares Celia Maria de Almeida CM Birren Bruce W BW Cuomo Christina A CA

PLoS genetics 20111027 10

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 brasilie ...[more]

PMID: 22046142

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Project description:Abstract: Candida parapsilosis and Candida albicans are human fungal pathogens that belong to the CUG clade in the Saccharomycotina. In contrast to C. albicans, relatively little is known about the virulence properties of C. parapsilosis, a pathogen particularly associated with infections of premature neonates. We describe here the construction of >200 C. parapsilosis strains carrying double allele deletions of transcription factors, protein kinases and species-specific genes. Two independent deletions were constructed for each target gene. Growth in > 40 conditions was tested, including carbon source, temperature, and the presence of antifungal drugs. The phenotypes were compared to C. albicans strains with deletions of orthologous transcription factors. We found that many phenotypes are shared between the two species, such as the role of Upc2 as a regulator of azole resistance. Others are unique. For example, Cph2 plays a role in the hypoxic response in C. parapsilosis and not in C. albicans. We found extensive divergence between the biofilm regulators of the two species. We identified 7 transcription factors and one protein kinase that are required for biofilm development in C. parapsilosis. Only three (Efg1, Bcr1, and Ace2) have similar effects on C. albicans biofilms, whereas Cph2, Czf1, Gzf3 and Ume6 have major roles in C. parapsilosis only. In addition, two transcription factors (Brg1 and Tec1) with well-characterized roles in biofilm formation in C. albicans do not have the same function in C. parapsilosis. We also compared the transcription profile of C. parapsilosis and C. albicans biofilms. Our analysis suggests the processes shared between the two species are predominantly metabolic. C. parapsilosis mRNA profiles of wild type (WT) at 37 degree celcius in planktonic growth conditions and ace2-/-, cph2-/-, efg1-/-, czf1-/-, ume6-/-, bcr1-/- and WT in biofilm conditions were generated by deep sequencing, in triplicate, using Illumina HiSeq2000.

Dataset Information

Comparative genomic analysis of human fungal pathogens causing paracoccidioidomycosis.

Publications

Comparative genomic analysis of human fungal pathogens causing paracoccidioidomycosis.

Similar Datasets

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