Comparative Genomic Analysis of Human Fungal Pathogens Causing Paracoccidioidomycosis

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.National Institute of Allergy and Infectious Diseases (U.S.)National Institutes of Health. Department of Health and Human Services (contract HHSN266200400001C)National Institutes of Health. Department of Health and Human Services(contract HHSN2722009000018C)Brazil. National Council for Scientific and Technological Developmen

Genus Paracoccidioides: Species Recognition and Biogeographic Aspects

Background: Paracoccidioidomycosis is a systemic mycosis caused by Paracoccidioides brasiliensis (species S1, PS2, PS3), and Paracoccidioides lutzii. This work aimed to differentiate species within the genus Paracoccidioides, without applying multilocus sequencing, as well as to obtain knowledge of the possible speciation processes. Methodology/Principal Findings: Single nucleotide polymorphism analysis on GP43, ARF and PRP8 intein genes successfully distinguished isolates into four different species. Morphological evaluation indicated that elongated conidia were observed exclusively in P. lutzii isolates, while all other species (S1, PS2 and PS3) were indistinguishable. To evaluate the biogeographic events that led to the current geographic distribution of Paracoccidioides species and their sister species, Nested Clade and Likelihood Analysis of Geographic Range Evolution (LAGRANGE) analyses were applied. The radiation of Paracoccidioides started in northwest South America, around 11–32 million years ago, as calculated on the basis of ARF substitution rate, in the BEAST program. Vicariance was responsible for the divergence among S1, PS2 and P. lutzii and a recent dispersal generated the PS3 species, restricted to Colombia. Taking into account the ancestral areas revealed by the LAGRANGE analysis and the major geographic distribution of L. loboi in the Amazon basin, a region strongly affected by the Andes uplift and marine incursions in the Cenozoic era, we also speculate about the effect of these geological events on the vicariance between Paracoccidioides and L. loboi. Conclusions/Significance: The use of at least 3 SNPs, but not morphological criteria, as markers allows us to distinguish among the four cryptic species of the genus Paracoccidioides. The work also presents a biogeographic study speculating on how these species might have diverged in South America, thus contributing to elucidating evolutionary aspects of the genus Paracoccidioides

Paracoccidioidomicosis y Paracoccidioides brasiliensis

Paracoccidioides brasiliensis es un hongo dimórfico patógeno, causante de la micosis sistémica más frecuente en América Latina, única región geográfica en la que se encuentra este agente. La característica dimórfica, es decir, su capacidad de mudar de una fase micelial (M) saprófita a 23º C (Figura 1a) a una fase levaduriforme (L) a 37º C (Figura 1b), está relacionada con la patogenicidad, no sólo en P. brasiliensis sino también en otros hongos patógenos como Histoplasma capsulatum y Blastomyces dermatitidis. Hay factores nutricionales y de temperatura que modulan este fenómeno. En el caso de P. brasiliensis, el cambio de temperatura es el único requisito para iniciar el proceso dimórfico [1]. La mayoría de las personas infectadas sólo desarrollan una paracoccidioidomicosis (PCM) asintomática o subclínica, la cual puede progresar hacia una enfermedad con múltiples formas clínicas [2], que dependen de factores en el huésped o ambientales y de la virulencia fúngica [3]. Una reactividad muy alta a la paracoccidioidina (60-75%) en la población adulta de regiones endémicas, apunta a cifras cercanas a los 10 millones de personas infectadas en América del Sur, aunque sólo es una fracción la que desarrolla la enfermedad [4]. Aun cuando el contacto con P. brasiliensis es esencialmente el mismo para personas de cualquier sexo, la PCM es, de 13 a 87 veces, más frecuente en hombres que en mujeres, por lo cual se presume la existencia de condiciones hormonales influyendo en el desarrollo de la dolencia [5]

Paracoccidioides brasiliensis, agente causal de una micosis sistémica de alta prevalencia en América Latina

La paracoccidioidomicosis es una micosis sistémica humana causada por el hongo dimórfico Paracoccidioides brasiliensis.Paracoccidioidomycosis is a human systemic mycosis caused by the dimorphic fungus Paracoccidioides brasiliensis

La micología médica en América latina.

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