Bug Bites and Malaria, the cause of one protein?

When people imagine a bug, mosquitoes often come to mind. After all, they are synonymous with hot days as a scourge, plaguing others with itchy bug bites. Despite their small size, mosquitoes are extremely dangerous. They often carry a plethora of diseases that could injure or even kill those infected. Dengue, yellow fever, West Nile virus, Zika, and Malaria, all types of mosquito-transmitted illnesses, kill approximately one million people each year. In the past, a staggering 50% of all human deaths since the rise of humanity have been linked to mosquitoes. In fact, during major wars throughout history, these mosquito-borne diseases played a critical role. During Pacific campaigns of World War II, Malaria decided battles as soldiers were infected by mosquitoes and died before fights.

Mosquitoes carry these diseases as a result of microorganisms that get transmitted. These pathogens get passed when mosquitoes feast on a vertebrate’s blood and inject their own saliva into the bloodstream. This action inhibits blood clotting by preventing platelets, cells that form clots to stop bleeding, from aggregating around a wound. In addition, a mosquito’s saliva exacerbates the severity of the disease they carry. Research has displayed that the saliva can enhance the infectivity and speed up the disease progression of Malaria. Mosquito saliva has been reported to contain around 40 unknown proteins that haven’t been fully discovered or researched by scientists. One particular protein named SGS1 is required for the growth of parasites carried by mosquitoes. Other studies demonstrated that SGS1 is positively linked with Zika virus. Due to unknown factors surrounding the protein regions of SGS1, it’s difficult for scientists to discover the nature of pathogen transmission via this saliva protein. The goal of the researchers in this study was to image and identify the proteins, such as SGS1, that are found within a mosquito’s saliva.

In order to accomplish this, they dissected around 50 mosquitoes and extracted their salivary glands, taking samples of the saliva and running them through machinery to analyze their biological components. From there, the scientists constructed models of their protein structure and attempted to identify how those specific proteins affect pathogen transmission. 

Their protein analysis revealed that SGS1 is the largest and most abundant protein found within the mosquitoes’ saliva (made up around 24%). Their structure analysis found that the SGS1 has a cocoon-shaped figure with 6 protein domains, or regions. From this, the scientists were able to relate SGS1 with a few other proteins that shared the same domains. Though, they did note that the domains in SGS1 are larger compared to the others. In addition, these domains were revealed to play a key role in protein-protein interactions that occur during mosquito pathogen transmission. Essentially, they are crucial in facilitating parasite invasion and also modulate the host’s immune response. It was also revealed that SGS1 contains a hydrophobic, or water repelling, layer that protects it from dissolving within the mosquito’s saliva. There are also protein chains called helices that detach after mosquito injection, binding to nearby cells. 

Based on their discoveries, the researchers concluded that SGS1 is extremely important for the transmission of pathogens and viruses by a mosquito. Thus, more experimentation needs to be done specifically on this salivary protein in the future. 

Citations:

Liu, S., Xia, X., Calvo, E., & Zhou, Z. H. (2023). Native structure of mosquito salivary protein uncovers domains relevant to pathogen transmission. Nature communications, 14(1), 899. https://doi.org/10.1038/s41467-023-36577-y

Köseoğlu, A. E., Paltacı, S., Can, H., Giantsis, I. A., Güvendi, M., Demir, S., Döşkaya, M., & Ün, C. (2023). Applicability evaluation of mtDNA based molecular identification in mosquito species/subspecies/biotypes collected from Thessaloniki, Greece. Veterinary parasitology, regional studies and reports, 41, 100869. https://doi.org/10.1016/j.vprsr.2023.100869