Scientists identify key regulator of malaria parasite transmission


Date:
February 25, 2022
Source:
Weill Cornell Medicine
Summary:
Malaria symptoms occur once the parasite's asexual stages
begin replicating inside red blood cells. However, these
asexual forms must transform into male and female stages called
gametocytes in order to infect the mosquitoes that spread the
disease. Investigators now report they have identified a protein
called HDP1 that plays a critical role in activating genes required
for the development of these male and female stages. The finding
provides important new insights into how the parasite controls
this conversion into gametocytes.



FULL STORY ========================================================================== Malaria remains one of the biggest global public health challenges. It
kills a young child every two minutes, more than any other infectious
disease.


========================================================================== Malaria parasites, of which Plasmodium falciparum is the most widespread
and lethal, are transmitted by mosquitoes and have a complex life
cycle. Malaria symptoms occur once the parasite's asexual stages begin replicating inside red blood cells. However, these asexual forms must
transform into male and female stages called gametocytes in order to
infect the mosquitoes that spread the disease.

In a study published Jan. 27 in Nature Microbiology, investigators from
Weill Cornell Medicine report they have identified a protein called
HDP1 that plays a critical role in activating genes required for the development of these male and female stages. The finding provides
important new insights into how the parasite controls this conversion
into gametocytes.

"HDP1 is essential for the development of the parasite's transmissible
stages," said senior author Dr. Bjo"rn Kafsack, assistant professor of microbiology and immunology at Weill Cornell Medicine.

Previous research has shown that switching between the different
stages requires the master gene regulator AP2-G, which initiates the development of the transmissible stages by activating other regulators
of gene expression, including HDP1.

In their new study, the researchers showed that HDP1 is required for
the parasite's maturation to the gametocyte stage, the first time such a connection has been shown. They used CRISPR/Cas9 gene-editing technology
to delete the hdp1 gene in P. falciparum parasites. Using microscopy
and other lab techniques, including flow cytometry and RNA sequencing
and chromatin profiling, they were able to discover what was happening
inside these cells at the molecular level.

They found that without HDP1, parasites were unable to turn up expression
of genes that are necessary to assemble mature gametocytes and give them
their characteristic sickle shape. This eventually leads to the death
of these gametocytes and leaves them unable to infect mosquitoes.

"HDP1 is the first of a previously uncharacterized class of DNA-binding proteins identified in malaria," said first author Dr. Riward Campelo
Morillo, a research associate in microbiology and immunology in the
Kafsack lab. "It provided us with a greater understanding of how genes
are regulated in these parasites." The team aims to further study how
these molecular changes cause the parasite to take on its sickle shape, something that is not currently known.

"By understanding the developmental program of these transmission
stages, it could eventually lead to possible future drugs for blocking transmission," Dr.

Kafsack said. "We may be able to find additional components of this
process that are unique to these parasites for us to target with drugs." ========================================================================== Story Source: Materials provided by Weill_Cornell_Medicine. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Riward A. Campelo Morillo, Xinran Tong, Wei Xie, Steven Abel,
Lindsey M.

Orchard, Wassim Daher, Dinshaw J. Patel, Manuel Llina's, Karine
G. Le Roch, Bjo"rn F. C. Kafsack. The transcriptional regulator
HDP1 controls expansion of the inner membrane complex during early
sexual differentiation of malaria parasites. Nature Microbiology,
2022; 7 (2): 289 DOI: 10.1038/s41564-021-01045-0 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220225100249.htm

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