Team:NAU-CHINA/Description
Known as one of the three hard-to-cure infectious diseases in the world, along with AIDS and tuberculosis, malaria is typically mosquito-borne and mainly transmitted by the bite of female Anopheles mosquitoes infected with Plasmodium.
Why do we choose our project ?
Known as one of the three hard-to-cure infectious diseases in the world, along with AIDS and tuberculosis, malaria is typically mosquito-borne and mainly transmitted by the bite of female Anopheles mosquitoes infected with Plasmodium[1].
In 2017, malaria popularized in 87 countries, risked half of the population’s health, and caused 435 thousand deaths in the world. Being shocked and impressed with the powerful invasive ability of these cruel parasites, we feel urged to relieve this situation with our own effort.
Previous treatments
Malaria averting starts with blocking the only media--mosquitoes. Two most widely-accepted and effective means of blocking the spread of malaria are as follows:
1. Insecticide-treated mosquito nets[2]: play the role of a physical barrier and have insecticidal effect.
2. Indoor spraying with residual insecticides[2]: have the insecticidal effect.
Instead of killing the Plasmodium directly, the treatments that we mentioned above are trying to eliminate all the mosquitoes. However, it is difficult to wiping out all of them since insecticides will leave intact the biological niche where mosquitoes reproduce[3]. Besides, even eliminating all the mosquitoes itself is not that safe, since mosquitoes are a part of our mother nature, removing all of them may cause a series of problems.
So, we explored the life cycle of Plasmodium by literature retrieval and hoped to find a better solution.
Life cycle
Life cycle of Plasmodium in the mosquito[4].
The 1st phase: Transmission starts when the mosquito ingests an infected blood meal (0 h). 0 h The mosquito ingests an infected blood meal. Within minutes, gametocytes develop into gametes (the star-shaped figure illustrates exflagellation, which is the formation of male gametes) that fuse to form the zygote that differentiates into a motile ookinete. Minutes later Gametocytes develop into gametes. Gametes fuse to form the zygote. The zygote differentiates into a motile ookinete. At 24 h, the ookinete invades the midgut epithelium and differentiates into an oocyst. Around 24 h The ookinete invades the midgut epithelium and differentiates into an oocyst. 2 weeks later The oocyst ruptures, releasing thousands of sporozoites into the mosquito body cavity (hemocoel).
The 2nd phase: The salivary gland is the only tissue that can be invaded, among all the tissues sporozoites contact. The mosquito bites another vertebrate host. The sporozoites release from the salivary glands. Transmission is completed.
During the rapid and … development of mighty Plasmodium, a bottleneck is detected in the mosquito’s midgut. Although female mosquito ingests thousands of gametophytes when biting, only about 10% of them successfully develop into zygotes, and only 5 zygotes will successfully invade the midgut epithelium to form oocysts. The oocysts mature and then release mass spore parasites.
Our Plan
Being inspired by Sibao Wang, from the Chinese Academy of Sciences(CAS), who engineered the symbiotic bacteria to secret peptides, the NAU-CHINA hopes to optimize this system with synthetic biology method. We create a more modular and regulated gene pathway in Serratia marcescens, which can colonize in the midgut of mosquitoes easily. It can release the fusion protein of nine anti-Plasmodium peptides to kill the Plasmodium in their most vulnerable stage. Besides, the Tobacco Etch Virus protease (TEVp) is used for its high efficiency and specificity, to cleave the fusion protein.
References
[1] Gong Zhenyu, Gong Xunliang. Overview of Global Malaria Prevention and Control in 2015[J]. Disease Surveillance, 2016, 31(2): 174-176.
[2] https://www.who.int/news-room/fact-sheets/detail/malaria
[3] Wang S , Jacobs-Lorena M . Genetic approaches to interfere with malaria transmission by vector mosquitoes[J]. Trends in Biotechnology, 2013, 31(3):185-193..
[4] Ghosh A , Srinivasan P , Abraham E G , et al. Molecular strategies to study Plasmodium–mosquito interactions[J]. Trends in Parasitology, 2003, 19(2):94-101.