Messing around with malaria
Anopheles gambiae mosquitoes are the principal vectors of human malaria, a disease with devastating consequences for public health and the economic development of disease-endemic countries. The creation of new tools to control vector populations is a focal point of intensive efforts to eradicate the burden of malaria. As mosquitoes generally copulate only once during their lives, interfering with the mating process is a promising avenue for research into vector control. Unfortunately, very little is known about the molecular or physiological basis of mating and insemination in malaria vectors. Of particular concern is our lack of knowledge about factors and pathways ensuring male reproductive success, such as those that result in sperm storage, oviposition, and the inhibition of remating in females. Improving our understanding of mating biology might not only inform currently proposed strategies for vector control, but could potentially allow the development of entirely novel tools for combating malaria.
Stopping male mosquitoes from sealing their sperm inside females with a ‘mating plug’ could prevent mosquitoes from reproducing, and offer a potential new way to combat malaria. The new study focuses on An. gambiae, the species of mosquito primarily responsible for the transmission of malaria in Africa. These mosquitoes mate only once in their lives, which means that disrupting the reproductive process offers a good way of dramatically reducing their populations. When these mosquitos mate, the male transfers sperm to the female and then afterwards transfers a coagulating mass of proteins and seminal fluids known as a mating plug. This plug is not found in any other species of mosquito and until now, very little was known about the role it plays in An. gambiae reproduction. The authors show that the mating plug is essential for ensuring that sperm is correctly retained in the female’s sperm storage organ, from where she can fertilise eggs over the course of her lifetime. Without the mating plug, sperm is not stored correctly, and fertilisation cannot occur.
The researchers analysed the composition of the protein-rich mating plug and discovered that it is formed when an enzyme called transglutaminase interacts with other proteins in the male mosquito’s seminal fluid. This interaction causes the seminal fluids to coagulate into a gelatinous solid mass. When the research team removed this enzyme in male mosquitoes in the lab, the fluids failed to coagulate and form the plug. Furthermore, when these males, lacking the key protein and therefore the plug, mated with females, reproduction was not successful. The male mating plug is not a simple barrier to insemination from rival males, as has been previously suggested. Instead, the plug plays an important role in allowing the female to successfully store sperm in the correct way inside her, and as such is vital for successful reproduction. If in the future we can develop an inhibitor that prevents the coagulating enzyme doing its job inside male An. gambiae mosquitoes in such a way that can be deployed easily in the field – for example in the form of a spray as it is done with insecticides – then we could effectively induce sterility in female mosquitoes in the wild. This could provide a new way of limiting the population of this species of mosquito, and could be one more weapon in the arsenal against malaria.
Transglutaminase-Mediated Semen Coagulation Controls Sperm Storage in the Malaria Mosquito. 2009 PLoS Biol 7(12): e1000272. doi:10.1371/journal.pbio.1000272
Insect seminal fluid proteins are powerful modulators of many aspects of female physiology and behaviour including longevity, egg production, sperm storage, and remating. The crucial role of these proteins in reproduction makes them promising targets for developing tools aimed at reducing the population sizes of vectors of disease. In the malaria mosquito Anopheles gambiae, seminal secretions produced by the male accessory glands (MAGs) are transferred to females in the form of a coagulated mass called the mating plug. The potential of seminal fluid proteins as tools for mosquito control demands that we improve our limited understanding of the composition and function of the plug. Here, we show that the plug is a key determinant of An. gambiae reproductive success. We uncover the composition of the plug and demonstrate it is formed through the cross-linking of seminal proteins mediated by a MAG-specific transglutaminase (TGase), a mechanism remarkably similar to mammalian semen coagulation. Interfering with TGase expression in males inhibits plug formation and transfer, and prevents females from storing sperm with obvious consequences for fertility. Moreover, we show that the MAG-specific TGase is restricted to the anopheline lineage, where it functions to promote sperm storage rather than as a mechanical barrier to re-insemination. Taken together, these data represent a major advance in our understanding of the factors shaping Anopheles reproductive biology.
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Tags: Africa, Biology, Health, Malaria, Medicine, Microbiology, Parasitology, Science
