Abstract
Pythium insidiosum is a human-pathogenic oomycete. Many patients infected with it lose organs or die. Toward the goal of developing improved treatment options, we want to understand how Py. insidiosum has evolved to become a successful human pathogen. Our approach here involved the use of comparative genomic and other analyses to identify genes with possible functions in the pathogenicity of Py. insidiosum. We generated an Oomycete Gene Table and used it to explore the genome contents and phylogenomic relationships of Py. insidiosum and 19 other oomycetes. Initial sequence analyses showed that Py. insidiosum is closely related to Pythium species that are not pathogenic to humans. Our analyses also indicated that the organism harbours secreted and adhesin-like proteins, which are absent from related species. Putative virulence proteins were identified by comparison to a set of known virulence genes. Among them is the urease Ure1, which is absent from humans and thus a potential diagnostic and therapeutic target. We used mass spectrometric data to successfully validate the expression of 30% of 14,962 predicted proteins and identify 15 body temperature (37 °C)-dependent proteins of Py. insidiosum. This work begins to unravel the determinants of pathogenicity of Py. insidiosum.
Highlights
Other species[6,7,8,9,10,11]
As a human and animal pathogen[11], Py. insidiosum must have evolved a special set of genes that are required for this pathogenesis, which are not found in other oomycetes
We analyse the genome content of Py. insidiosum, in comparison with that of 19 other oomycetes and 2 diatoms, to identify putative virulence genes, and shed light on the pathogenicity-related evolution of this pathogen
Summary
Other species[6,7,8,9,10,11]. Py. insidiosum is an invasive pathogen of nonhuman animals, such as horses, dogs, cats and cattle[11]. The genome of Py. insidiosum is 53.2 Mb in size and comprises 14,962 predicted open reading frames This sequence information provides a useful resource for exploring the biology, evolution and pathogenicity of Py. insidiosum. Since the ability to grow at the host’s body temperature is essential for an invasive pathogen, we incorporated newly generated mass spectrometric data to validate and identify Py. insidiosum proteins that are differentially expressed in response to a shift in temperature from 25 °C to 37 °C. These studies have begun to reveal the factors behind the pathogenicity of Py. insidiosum
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