Plasmodium

Plasmodium is a genus of single-celled organisms that must live as parasites, infecting both vertebrates and insects—most often mosquitoes from the genus *Anopheles*. The parasite’s life cycle begins when an infected insect takes a blood meal and injects the parasites into a vertebrate host. Inside the vertebrate, the parasites first develop in a body tissue, frequently the liver, before moving into the bloodstream to invade red blood cells. The destruction of these red blood cells can cause the disease malaria. During a blood infection, some parasites are taken up by another blood-feeding insect—usually a mosquito—which then continues the cycle.

This genus belongs to the phylum Apicomplexa, a large group of parasitic eukaryotes, and within that to the order Haemosporida and family Plasmodiidae. More than 200 species of *Plasmodium* have been described, divided into 14 subgenera based on their physical traits and the hosts they infect. However, evolutionary relationships often do not match these taxonomic groupings; some species that look alike or infect the same host are actually not closely related.

*Plasmodium* species are found worldwide wherever suitable hosts exist. Insect hosts are most often mosquitoes from the genera *Culex* and *Anopheles*, while vertebrate hosts include reptiles, birds, and mammals. The parasites were first identified in the late 1800s by Charles Laveran. Over the 1900s, many more species were discovered in various hosts and classified, including five that regularly infect humans: *P. vivax*, *P. falciparum*, *P. malariae*, *P. ovale*, and *P. knowlesi*. Of these, *P. falciparum* is the most deadly, causing hundreds of thousands of human deaths each year. Several drugs have been developed to treat *Plasmodium* infections, but the parasites have evolved resistance to every one. Infection through blood transfusion is possible but very rare, and the parasite cannot spread directly from person to person. Some subspecies are obligate intracellular parasites.

All *Plasmodium* species are eukaryotes in the phylum Apicomplexa that undergo a type of asexual replication called merogony inside host red blood cells and produce the pigment hemozoin as a byproduct of digesting hemoglobin. They share many features with other eukaryotes, along with some unique to their group. The genome is housed in the nucleus on 14 chromosomes. For most of the life cycle, the parasite keeps a single copy of its genome, doubling it only during a brief sexual exchange inside the insect host’s midgut. Attached to the nucleus is the endoplasmic reticulum, which works similarly to that in other eukaryotes. Proteins move from the ER to the Golgi apparatus, which in apicomplexans is usually a single membrane-bound compartment, and from there to other parts of the cell or the surface.

Like other apicomplexans, *Plasmodium* has several specialized structures at its apical end used to secrete effectors into the host. The largest are the bulbous rhoptries, which contain proteins for invading host cells and modifying them afterward. Next to these are smaller micronemes, which hold proteins needed for movement and for recognizing and attaching to host cells. Scattered throughout the parasite are dense granules—secretory vesicles containing proteins that modify the membrane of the parasitophorous vacuole, the compartment that separates the parasite from its host.

*Plasmodium* species also have two large membrane-bound organelles that came from endosymbiosis: the mitochondrion and the apicoplast. Unlike mammalian cells, which have many mitochondria, *Plasmodium* has a single large mitochondrion that divides in sync with the cell. It can generate ATP through the citric acid cycle, but this function is only needed for survival in the insect host, not for growth inside red blood cells. The apicoplast came from a secondary endosymbiosis, when an ancestor of *Plasmodium* acquired a red alga. This organelle helps make various metabolic precursors, including fatty acids, isoprenoids, iron-sulfur clusters, and parts of the heme biosynthesis pathway.

The life cycle includes several distinct stages in both the insect and vertebrate hosts. Parasites are usually introduced into a vertebrate by the bite of an insect host—mostly a mosquito, except for some reptile-infecting species. They first infect the liver or other tissue, where they undergo one large round of replication before leaving to infect red blood cells. In some primate-infecting species, a dormant stage called a hypnozoite can form, staying in the liver for over a year. For most species, however, the parasites in liver cells are simply merozoites. After leaving the liver, they enter red blood cells and go through continuous cycles of infection. A small percentage of parasites turn into a sexual stage called a gametocyte, which is picked up by an insect host during a blood meal. In some hosts, the invasion of red blood cells can cause the disease malaria.