In a Mosquito
Parasite Development in a Mosquito
In the Mosquito
The zygote forms in a mosquito, so the mosquito is called the definitive host for Plasmodium falciparum. The following describes four stages of parasite development in the mosquito from the blood meal to the bite.
The zygote marks the beginning of the parasite’s life cycle, but to tell the story, we must go back just a bit to the end. A zygote forms when at least one macrogametocyte (female) and one microgametocyte (male) are present in a blood meal. While enzymes are digesting the blood, the zygote forms in the lumen (the interior space) of the mosquito mid gut. (We will come back to formation of gametocytes in humans at the end.)
The gametocytes are initially enveloped in the membrane of the red blood cell they infected in the human host. The microgametocyte exflagellates, the macrogametocyte sheds its protein coat, and the gametocytes become gametes. The microgamete finds a macrogamete, and they fuse to form a zygote.
- How does a microgamete find a macrogamete? [@LawniczakMKN2016ComputationalLens]
The Zygote
The zygote stage is short; the whole process takes less than 24 hours, and there is only one round of replication: two cells (a microgametocyte and a macrogametocyte) fuse, and create a single ookinete with four distinct haploid gemomes. The ookinete invades the cells of the mid gut.
The zygoes stage is critical, however, for parasite genetics. It is important to understand that parasites can recombine sexually, and that each zygote can produce four distinct haploid genomes. The zygote is the only parasite life stage that is diploid.
This process of sexual recombination in parasites doesn’t work exactly the same way a it does in mammals, or other organisms that are [@GutteryDS2023MeiosisPlasmodium]. In other organisms, the point of meiosis is to produce haploid gametes from a diploid cell. In Plasmodium, meiosis occurs directly after after fertilization in the developing zygote. To put it in other terms, humans spend decades as diploid organisms. The human germ line – sperm and eggs – are both diploid cells that are carried around inside us, separate from the somatic cells. At fertilization, two diploid cells fuse.
The process is different in parasites, because the parasite spends almost all of its time haploid. After fertilization, the parasite becomes diploid and remains diploid for only a few hours. The zygote DNA (2N) is duplicated (i.e., pre-meiotic replication) to form a tetraploid cell (4N), followed by two rounds of chromosome segregation to form four discrete haploid genomes, contained within a single nucleus in the fully mature ookinete. The process takes less than 24 hours.
For parasite genetics, the relationship between the microgametocyte and macrogametocyte matter. If the gametes are clones, then the four haploid cells can have different combinations of the somatic mutations that accumulated from mutations acquired at some point in development since the last zygote.
While the mature ookinete thus contains four distinct genomes, later events in the oocyst might change the balance.
- Meiosis in Plasmodium: how does it work? [@GutteryDS2022DivisionTransmission; @GutteryDS2023MeiosisPlasmodium]. (Fig. 1, from the second article) contrasts meiosis in mammals, Schizosaccharomyces pombe, and Plasmodium.
The Ookinete
A motile, banana-shaped form that develops in the mosquito midgut lumen as the final stage of meiosis. The ookinete invades the midgut epithelium and becomes an oocyst.
The ookinete invades the mosquito gut wall and develops into an oocyst where endomitosis (sporogony) results in the production of hundreds of haploid sporozoites that will migrate to the mosquito’s salivary glands to infect the vertebrate host.
The Oocyst
A thick-walled parasite life-stage embedded in the midgut epithelium.
The time elapsed from the blood meal to the formation of an oocyst is typically 18-24 hours.
Inside the oocyst, hundreds of parasites form. The process is called sporogony.
- What is the distribution of the number of oocysts per mosquito? [@SaulA2008EfficacyModel]
Sporozoites
Sporozoites migrate through the mosquito homocoel into the mosquito salivary glands. Once the sporozoites are found in the mosquito salivary glands, the mosquito is presumed to be infectious.