New discovery: Chinese scientists have discovered the core regulator of malaria transmission

After maintaining zero local malaria cases for three consecutive years, China applied for malaria-free certification from the World Health Organization (WHO) last year.
A few days ago, the WHO officially announced that China has become the 40th country in the world to completely eradicate malaria, and it is also the most eradicated country.
In a country with malaria, this is undoubtedly a great achievement
.

However, looking at the world, malaria is still a major public health problem facing the world.
There are more than 200 million malaria infections and 400,000 deaths, most of which are children
.

The pathogen of malaria is Plasmodium.
The growth of Plasmodium requires two hosts: human and Anopheles.
Only mature gametophytes can be transmitted by Anopheles mosquitoes.
Therefore, gametogenesis of Plasmodium is a key link in malaria transmission
.

On August 8, 2021, Tongji University and Jiangsu Institute of Parasitic Disease Control jointly published an article entitled "A cascade of transcriptional repression determines sexual commitment and development in Plasmodium falciparum" in the international journal Nucleic Acids Resreach, revealing The core regulator of malaria transmission
.

DOI: https://hub.
pubmedplus.
com/10.
1093/nar/gkab683

First, the research team used CRISPR-Cas9 gene editing technology to carry out systematic gene knockout and gametophyte production ability screening of the P.
falciparum ApiAp2 transcriptional regulator family (the main regulators of the sexual behavior of human and rodent malaria parasites)
.

Functional screening of ApiAP2 family for gametophyte production

Subsequently, the researchers studied the function and mechanism of PfAP2-G5.
Through experiments such as chromatin immunoprecipitation and differential transcriptome analysis, the target genes and regulatory mechanisms of PfAP2-G5 were identified.
The results showed that PfAP2-G5 can be combined with The upstream region and the exon gene body combine to inhibit the transcriptional activity of pfap2-g (the key gene for plasmodium sex conversion).
The exon gene body is related to the maintenance of the local heterochromatin structure, thereby preventing the occurrence of sexual behavior and making the plasmodium.
No sexual conversion, only asexual reproduction in the body
.

PfAP2-G5 inhibits the transcriptional activity of pfap2-g gene

Finally, the researchers also proved through experiments that PfAP2-G5 also plays an important role in the development of early gamete cells.
In the G0 stage of the plasmodium sex transition, PfAP2-G can up-regulate PfAP2-G5 and other target genes, so that pfap2-g5 is in The G0 stage reaches the maximum transcription and promotes the development of early gametophytes; however, when the Plasmodium develops to the G1 stage, PfAP2-G5 can combine with PfAP2-G2 to rapidly inhibit PfAP2-G and its target genes, which are related to early gametophytic development.
The rapid closure of the gametophyte is the key to maturation of the gametophyte
.

Experimental mechanism diagram

In conclusion, this article found that PfAP2-G5 is indispensable in gametogenesis
.

Reference materials:

[1]https://academic.