Pearls Genomic Insights into the Fungal Pathogens of the Genus Pneumocystis: Obligate Biotrophs of Humans and Other Mammals

Pneumocystis organisms were first believed to be a single protozoan species able to colonize the lungs of all mammals. Subsequently, genetic analyses revealed their affiliation to the fungal Taphrinomycotina subphylum of the Ascomycota, a clade which encompasses plant pathogens and free-living yeasts. It also appeared that, despite their similar morphological appearance, these fungi constitute a family of relatively divergent species, each with a strict specificity for a unique mammalian species [1]. The species colonizing human lungs, Pneumocystis jirovecii, can turn into an opportunistic pathogen that causes Pneumocystis pneu-monia (PCP) in immunocompromised individuals, a disease which may be fatal. Although the incidence of PCP diminished in the 1990s thanks to prophylaxis and antiretroviral therapy, PCP is nowadays the second-most-frequent, life-threatening, invasive fungal infection worldwide, with an estimated number of cases per year above 400,000 [2]. Despite this clinical importance, studies of P. jirovecii progressed slowly, at least in part because of the lack of a continuous culture system. Nevertheless, recent genomic findings provided insights into the lifestyle of these fungi. Genome Sequences Despite the absence of culture, the nuclear genome sequences of three Pneumocystis spp. have been recently released to the public. That of P. carinii, the species infecting rats, was obtained from resected lungs of an infected rat and purification of P. carinii cells (pgp.cchmc.org). This provided sufficient amounts of relatively pure DNA for conventional cloning and sequencing of chromo-somes separated on gel, as well as for high throughput DNA sequencings (HTS). The nuclear genome sequence of P. murina, the species infecting mice, was obtained from resected lungs followed by HTS (Pneumocystis murina Sequencing Project