Comparative Genomics Suggests That the Human Pathogenic Fungus Pneumocystis jirovecii Acquired Obligate Biotrophy through Gene Loss

Abstract

Pneumocystis jirovecii is a fungal parasite that colonizes specifically humans and turns into an opportunistic pathogen in immunodeficient individuals. The fungus is able to reproduce extracellularly in host lungs without eliciting massive cellular death. The molecular mechanisms that govern this process are poorly understood, in part because of the lack of an in vitro culture system for Pneumocystis spp. In this study, we explored the origin and evolution of the putative biotrophy of P. jirovecii through comparative genomics and reconstruction of ancestral gene repertoires. We used the maximum parsimony method and genomes of related fungi of the Taphrinomycotina subphylum. Our results suggest that the last common ancestor of Pneumocystis spp. lost 2,324 genes in relation to the acquisition of obligate biotrophy. These losses may result from neutral drift and affect the biosyntheses of amino acids and thiamine, the assimilation of inorganic nitrogen and sulfur, and the catabolism of purines. In addition, P. jirovecii shows a reduced panel of lytic proteases and has lost the RNA interference machinery, which might contribute to its genome plasticity. Together with other characteristics, that is, a sex life cycle within the host, the absence of massive destruction of host cells, difficult culturing, and the lack of virulence factors, these gene losses constitute a unique combination of characteristics which are hallmarks of both obligate biotrophs and animal parasites. These findings suggest that Pneumocystis spp. should be considered as the first described obligate biotrophs of animals, whose evolution has been marked by gene losses.

The Host Microbiome Regulates and Maintains Human Health: A Primer and Perspective for Non-Microbiologists

“…An increasing number of gene transfer events among domains are being documented as well as across ecological niches (55-57). The genetic modification can be due to increases in genetic content but genetic loss also has critical consequences in competitiveness or niche settlement (58,59). As no clear general phylogenetic definition of strain has emerged in this era of genomics, efforts are to differentiate the different isolates with markers not yet found in other genomes and/or single nucleotide polymorphism (20,21,60,61).…”

Ericoid mycorrhizal fungi and their genomes: another side to the mycorrhizal symbiosis?

“…Extensive loss of genes encoding CAZymes and key enzymes in secondary metabolism characterises the genome of many specialised biotrophic plant pathogens (Kemen et al, 2011;Spanu, 2012). Gene loss is also observed in the evolution of biotrophy in human fungal pathogens, such as Pneumocystis jirovecii, where most amino acid and purine biosyntheses have been lost (Ciss e et al, 2014). A depauperate repertoire of CAZymes is found in Xylona heveae (Xylonomycetes, Ascomycetes), an HT fungal endophyte exclusively found in rubber trees (Gazis et al, 2016).…”

Purine Acquisition and Synthesis by Human Fungal Pathogens

“…The Pneumocystis pneumonia-causing fungus Pneumocystis jirovecii also lacks the catabolic enzymes required for the degradation of purines, although this is the only human fungal pathogen known to do so [42]. …”