What Causes Pneumocystis Pneumonia?

Pneumocystis pneumonia is a potentially life-endangering disease caused by the fungal pathogen Pneumocystis jiroveci. It is predominantly observed in immunocompromised individuals. This microorganism is the most common causative agent of opportunistic infections in patients who present with acquired immunodeficiency syndrome (AIDS) in developed countries.

The exact name of the species that infects humans has been amended from Pneumocystis carinii to Pneumocystis jirovecii in order to differentiate it from the species that infects and causes disease in rats. The name was given in honor of the Czech parasitologist Otto Jirovec who contributed substantially to the research on this organism.

A Fungus or a Parasite?

Pneumocystis jiroveci is a unicellular eukaryotic microorganism that is widespread and ubiquitous in geographic distribution. Initial researches indicated that this organism is a protozoon ( a single-celled organism with animal-like behavior). Some have suggested that it may be a protist of independent taxonomic position.

Still, such taxonomic positioning of Pneumocystis as a genus of unique protozoan organisms was disputed for several years. Today they are identified as fungi, based on their ribosomal ribonucleic acid (rRNA) and specific homologies of other gene sequences, as well as the composition of cell walls and the structure of their fundamental enzymes. Currently a vast majority of scientists group Pneumocystis jiroveci among ascomycetous yeasts. This is the same group in which Saccharomyces cerevisiae (brewer's yeast) is located.

The strains of this microorganism also show high genetic diversity, predominantly due to gene variations that stem from the presence of specific single-nucleotide polymorphisms. In addition, some polymorphisms are considered exceptionally informative markers that can be employed for comparative analyses between the genotype and specific epidemiological or clinical data.

Trophic Stages and Morphology

Pneumocystis jiroveci shows a biphasic life cycle and has two diverse morphological forms:

  • haploid trophozoites (which are a hallmark of the asexual, proliferative phase of its lifecycle)
  • cysts (which represent its sexual phase)

Cysts are produced during the reproductive stage due to the conjugation of trophozoites, while trophic forms prevail in lungs during the infection.

The primary proliferative life cycle of Pneumocystis jiroveci consists of minute, haploid (containing only one member of each chromosome pair) trophic forms that grow into bigger, diploid (containing two members of each chromosome pair) trophic forms and reproduce asexually by cell division. During ultrastructural studies, investigators have described the shape of the trophic form as pleomorphic or amoeboid. The shape of large trophic forms often appears quite irregular during electron microscopy.

Cysts represent an intrapulmonary life cycle stage of Pneumocystis jiroveci. These are developed from parent cells by meiosis and partitioning of the cytoplasm. The cysts are a thick-walled sexual (or reproductive) stage consisting of eight haploid progeny cells that show focal thickening of the wall. This is visible even by light microscopy in silver-stained specimens.

The nucleus of this fungal pathogen is small (between 0.5 and 1 µm), bounded by a typical nuclear envelope with pores, and contains a noticeable nucleolus. It is not completely clear if mitosis in Pneumocystis jiroveci is closed (fully contained within the nuclear envelope) or semi-open (with a partial breakdown of the nuclear envelope).

The mitochondria of Pneumocystis jiroveci are usually poorly preserved and they appear swollen. The analysis of serial sections of trophic forms has revealed a single mitochondrion that can be branched or that is irregular in shape. There are also Golgi-like vesicles, endoplasmic reticulum and primary lysosomes.

The early stages of Pneumocystis jiroveci proliferation inside the human organism prompt the activation of alveolar macrophages and an increase of proinflammatory cytokines, as well as changes in pulmonary surfactant. Such adjustments occur even when the infection process is characterized by lower fungal burden.

Reviewed by Liji Thomas, MD

References

Further Reading

Last Updated: Jan 5, 2017

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