October 30, 2013

New Molecular Target For Malaria Control Identified

Malaria is a leading cause of death in tropical and subtropical regions and it is transmitted by a bite from infected female mosquitoes. According to the U.S. Centers for Disease Control, malaria claims nearly 660,000 lives per year, 90% of them in Africa—and most of them children. There were an estimated 216 million malaria cases worldwide in 2010, mostly among pregnant women and children. Despite the efforts to develop a vaccine, there is still not an effective one thus other strategies, such as blocking egg development in malaria mosquito, could significantly reduce transmission of the disease.

Researchers at Harvard School of Public Health (HSPH) and University of Perugia (UNIPG) have shown that egg development in the mosquito species, primarily responsible for spreading malaria, depends on a switch in the female that is turned on by a male hormone delivered during sex. Blocking the activation of this switch could impair the ability of the species, Anopheles gambiae, to reproduce, and may be a viable future strategy for mosquito and malaria control. The study is published October 29, in the open access journal PLOS Biology.

"These findings represent a significant step forward in our understanding of how these devastating malaria vectors reproduce," said Flaminia Catteruccia, associate professor of immunology and infectious diseases at HSPH and UNIPG.

The researchers studied the interaction between a steroid hormone called 20-hydroxy-ecdysone, or 20E—which is transferred from the male to the female mosquito during mating—and a female "Mating-Induced Stimulator of Oogenesis," or MISO, protein (oogenesis is the process by which an egg cell is created).

They used chemical techniques to suppress MISO's functioning in female mosquitoes and found that doing so reduced egg development. They also found that MISO and 20E interact in the female mosquito's reproductive tract. Further, they identified the signalling pathway through which 20E affects MISO. The 20E-MISO interaction boosts the accumulation of fat in the ovaries, which is needed to fuel oogenesis, leading to a more rapid and higher production of eggs. Thus, the researchers concluded that egg development depends on this "switch," formed by 20E and MISO, which is turned on in the female when 20E is delivered during sex.

Male-transferred 20E essentially acts as a "mating signal" for the female to produce more eggs. "How males contributed to egg development had been previously unknown; with the identification of the molecular players of this male-female interaction we can now find ways to switch off the signal and prevent females from reproducing," said Catteruccia.

"This is the first time, in any insect species, that a male hormone has been shown to directly interact with a female protein and alter the ability of the female to reproduce", said co-author Francesco Baldini, a UNIPG graduate student who performed part of the analyses as a visiting scientist at HSPH.

The researchers claim this new finding holds promise for the development of new tools for controlling malaria-transmitting mosquito populations.


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