Is the unique camouflage strategy of Pneumocystis associated with its particular niche within host lungs?

The fungal genus Pneumocystis includes species that colonize mammalian lungs. If the immune system of the host weakens, these obligate parasites can turn into opportunistic pathogens causing deadly pneumonia. Each Pneumocystis species presents a strict specificity for a single mammalian species, although few exceptions may exist in rodents [1]. The lack of an established long-term method of in vitro cultivation for these fungi has considerably hindered their study. Nevertheless, the advent of high throughput methods allowed sequencing the genomes of Pneumocystis jirovecii, P. carinii, and P. murina, infecting, respectively, humans, rats, and mice [2,3]. The size of these genomes is approximately 8 Mb, their guanine-cytosine content is approximately 28%, and their number of chromosomes is approximately 17. However, the telomeres, subtelomeres, and centromeres remained elusive because their repetitive nature prevented assembling them. The subtelomeres of Pneumocystis species harbor genes encoding glycoproteins that are believed to be responsible for important virulence factors, i.e., surface antigenic variation and adhesion to host tissues [4–6]. Surface antigenic variation is thought to allow escape from the host immunity during colonization, and approximately 5% of each Pneumocystis genome is dedicated to this system. Antigenic variation is a common strategy among microbial mammalian pathogens. The systems often rely on gene families encoding surface antigens localized at subtelomeres; presumably because these genomic regions are prone to gene silencing and perhaps enhanced mutagenesis [7]. Moreover, the clusters of telomeres that are formed at the nuclear periphery during meiosis may favor ectopic recombinations, which can be responsible for the generation of new mosaic antigens [8]. The advent of a DNA sequencing method generating long reads recently allowed assembly of Pneumocystis subtelomeres and characterization of their gene content. This revealed their organization and new gene families encoding surface glycoproteins that constitute a superfamily. In this review, I update the understanding of the system and the strategy of antigenic variation of Pneumocystis species in the light of these new observations.