An organism with an identity crisis
In 1909, the Brazilian physician and scientist Carlos Chagas was investigating tropical diseases when he observed a strange microorganism in the lungs of lab animals. He initially misidentified it as a stage in the life cycle of Trypanosoma cruzi, the protozoan that causes Chagas disease. This case of mistaken identity would persist for decades. Two years later, Antonio Carini also found the organism in Brazil, and in 1912, researchers at the Pasteur Institute named it Pneumocystis carinii, still believing it to be a protozoan.
The organism's true nature remained hidden until the era of molecular genetics. Its life cycle stages resembled those of a protozoan, and it didn't respond to standard antifungal drugs. The definitive reclassification came in 1988, when analysis of its ribosomal RNA proved conclusively that Pneumocystis was not a protozoan but a highly unusual fungus belonging to the Ascomycota phylum. Further genetic studies revealed that the species found in rats (P. carinii) was distinct from the one that infects humans. To correct the record, the human-specific pathogen was renamed Pneumocystis jirovecii in honor of Czech parasitologist Otto Jírovec, who had identified it as the cause of pneumonia in infants back in 1952.
The making of an obligate parasite
Pneumocystis jirovecii is a example of reductive evolution. In adapting to its stable environment, the mammalian lung, it has shed genes essential for a free-living existence. The genome is small and lacks the instructions for making many of its own amino acids and vitamins, forcing it to scavenge these nutrients from its host. This complete dependence is why it has been impossible to grow P. jirovecii in a laboratory without living host cells.
Its cellular structure also reflects this parasitic lifestyle. Unlike most fungi, whose cell walls are full of a substance called ergosterol, P. jirovecii has a cell membrane that contains cholesterol. It is believed to absorb this cholesterol directly from its host. This biochemical quirk renders most antifungal drugs, which work by targeting ergosterol synthesis, completely ineffective.
This organism is found worldwide, and most people are exposed to it by the age of four, typically without any symptoms. In individuals with healthy immune systems, it exists as a harmless colonizer. In those with compromised immunity, such as organ transplant recipients or patients with HIV/AIDS, the fungus can multiply uncontrollably. This leads to Pneumocystis pneumonia (PCP), a severe lung infection that was one of the first and most common opportunistic illnesses seen at the start of the AIDS epidemic in the 1980s.