Researchers at Weill Cornell just lately printed a examine in Nature Microbiology that highlights the newly found intricacies of the malaria transmission cycle. The outcomes of their examine may have implications for the way scientists strategy malaria prevention sooner or later.
Malaria is a life-threatening illness transmitted by mosquitoes that disproportionately impacts tropical nations. In keeping with the Middle for Illness Management and Prevention, malaria is a number one explanation for loss of life and illness in low- and middle-income nations and stays a big world well being drawback.
The reason for malaria is a microscopic organism referred to as a protozoan — extra particularly the parasitic protozoan, plasmodium. This parasite lives in two completely different hosts: people and mosquitoes. Whereas there are 5 species of plasmodium that routinely trigger malaria in people, the species P. falciparum is most life-threatening, making it a positive analysis goal for labs like Kafsack’s.
When an contaminated mosquito bites an individual, it transmits a type of the parasite referred to as sporozoites to the human host. The sporozoites then journey by the blood vessels and infect liver cells, the place they reproduce asexually. The parasites then burst out of the liver cell in a brand new kind referred to as merozoites and enter the bloodstream, the place they aim purple blood cells. Inside purple blood cells, the merozoites kind a ring-like construction referred to as a trophozoite.
Most trophozoites reproduce asexually and launch extra merozoites into the bloodstream, however some carry out sexual replica, forming cells referred to as gametocytes. Whereas the asexual blood levels should not infectious to a mosquito, gametocytes are.
As a result of malaria is just not instantly transmitted between people, the parasite should return to a mosquito host to finish its transmission cycle — that is achieved by a blood meal, wherein the mosquito ingests the malaria parasites of their sexual kind from the human.
Whereas asexual replication retains the human host contaminated with malaria, sexual replication is essential for transmission to a mosquito host, and each are wanted to finish the malaria cycle.
The regulation of developmental transitions in these blood cells is the first focus of the paper’s senior writer, Prof. Björn Kafsack, microbiology and immunology. First writer Chantal Harris grad carried out a lot of the experiments for the examine in Kafsack’s lab, in line with Kafsack.
The way in which that gametocytes regulate their formation entails a transcription issue, AP2-G.
When AP2-G is turned on, permitting for gene expression, parasites grow to be gametocytes within the human host. When ingested by a mosquito, these gametocytes mediate the transmission of malaria to the mosquito host.
“Principally, the query is how does the parasite management what number of gametocytes it makes, or how typically does it flip a gene on,” Kafsack mentioned.
When chromatin — the constructing blocks of chromosomes fabricated from DNA and proteins — are very tightly packed, gametocytes can’t be shaped. When chromatin is just not packed densely sufficient, the gene is just not silenced correctly, leading to gametocyte formation.
Kafsack’s analysis stems from a separate 2017 examine, which discovered that lysoPC, a lipid biomolecule, suppresses P. falciparum’s gametocyte formation. Kafsack and his crew wished to search out the hyperlink between lysoPC and the AP2-G transcription issue.
The lab discovered that the parasite makes use of a choline molecule to create its membrane. LysoPC is used to synthesize the precursor for choline. Nevertheless, when the precursor is scarce, the parasite finds a brand new method to synthesize choline, consuming a molecule referred to as S-adenosylmethionine, or SAM, within the course of. The consumption of SAM impairs the dense packing of chromatin that’s wanted to silence AP2-G, which ends up in gametocyte formation.
“If the parasite has to make plenty of phosphocholine itself, the brake pads put on down on the silencing of AP2-G, so silencing turns into leaky, so that you make extra gametocytes,” Kafsack mentioned.
This conclusion offers perception into how gametocyte formation is regulated in malaria parasites.
The appliance of Kafsack’s analysis is basically illness prevention. Although altering gametocyte formation wouldn’t profit an already contaminated particular person, it may forestall the longer term unfold of the illness. As a result of P. falciparum is so adaptable to human and mosquito hosts, malaria has confirmed to be a really tough illness to deal with — nonetheless, Kafsack’s analysis sheds gentle on essential molecular mechanisms that regulate an infection.
“To cease transmission, we have to not solely deal with people who find themselves sick but additionally discover people who find themselves asymptomatic, as a result of asymptomatic carriers carry gametocytes,” Kafsack mentioned. “We’d like medication that kill the asexual levels, which is what provides individuals malaria, however we additionally want to search out methods of blocking transmission, and understanding how that works is what my lab does.”
Anna Labiner may be reached at [email protected].