Mosquito-borne infectious diseases are one of the most threatening infectious diseases to human health and life. Taking dengue fever and Zika fever, two of the most representative mosquito-borne infectious diseases, for example, dengue fever is endemic in more than 100 countries around the world, causing up to 390 million infections every year. Between 500,000 and 1 million people were hospitalized, and Zika virus led to a sudden outbreak of large outbreaks in the Pacific Islands and South America from 2015 to 2017, with more than 223,000 confirmed cases of Zika and thousands of cases of neonatal microcephaly in less than a year, and was declared a public health emergency of international concern by the International Health Organization. To date, there are no effective drugs and vaccines for most mosquito-borne viruses, and mosquito control measures have not been able to control the spread of mosquito-borne viruses. There is an urgent need for low-cost and environmentally friendly prevention and control strategies to stop the widespread spread of mosquito-borne viruses.
On April 19, the team of Professor Cheng Gong of the School of Basic Medical Sciences of Tsinghua University, together with the Yunnan Academy of Animal Science and Veterinary Sciences, Shenzhen BGI Life Science Research Institute and other teams, found a key environmental symbiotic bacteria that can determine the susceptibility of mosquitoes to viruses in Yunnan Province, China. The results of this study provide a new solution for the prevention and control of important mosquito-borne infectious diseases. The results of the research were published in the top international academic journal Science, which has brought revolutionary progress to this field.
Screenshot of Science's official website
The study found that colonizing the gut of Aedes albopictus and Aedes aegypti mosquitoes with a natural commensal bacterium called Rosenbergiella_YN46 was effective in blocking mosquito-borne flaviviruses, including dengue virus and Zika virus, which was confirmed in field experiments in Yunnan Province. Rosenbergiella_YN46 bacteria secrete a glucose dehydrogenase enzyme that rapidly acidifies the intestinal environment of blood-sucking mosquitoes (pH≈6.0), leading to the remodeling of the mosquito intestinal microenvironment. A large number of previous studies have shown that the envelope proteins of mosquito-borne viruses such as dengue virus are sensitive to acidic signals, and when the virus is in an acidic environment of pH <6.5, its envelope proteins will undergo irreversible allosterism, causing the virus particles to enter the state of uncapsid and lose their infectious activity. Therefore, the acidified intestinal environment can directly inactivate the viral particles that enter the intestine, thereby inhibiting the ability of mosquitoes to acquire viruses by sucking blood, and greatly reducing mosquito susceptibility to viruses. This discovery not only reveals the complex interaction between mosquito gut microbes and virus transmission, but also provides a new strategy for the prevention and control of mosquito-borne virus transmission.
Rosenbergiella_YN46 bacteria reshape the intestinal microenvironment of mosquitoes by secreting RyGDH factor, inhibiting blood-sucking mosquito infection and spreading the virus
The research team conducted large-scale metatranscriptome sequencing of the Aedes mosquito gut in several regions of Yunnan Province and found that there was a high correlation between the distribution of Rosenbergiella_YN46 bacteria in nature and the geographical distribution of dengue fever epidemic in Yunnan Province. The bacteria of the genus Rosenbergiella are all related to plant juice and nectar, and are widely used in the natural environment as environmental symbiotic bacteria. Yunnan Province is the main area where dengue fever and other virulent mosquito-borne infectious diseases are prevalent on the mainland. The results showed that there were significant heterogeneities and hotspots in dengue fever epidemics in different regions of Yunnan Province under the conditions of similar climatic environment and similar mosquito population density. According to epidemiological records in the past decade, there have been perennial outbreaks of dengue fever in Xishuangbanna and Lincang, but there are almost no local reports of dengue fever in the neighboring Wenshan and Pu'er. Therefore, the researchers went deep into the four regions to collect mosquitoes from locations with similar climatic and environmental factors, and to detect the colonization of Rosenbergiella_YN46 bacteria in the gut of mosquitoes in the wild.
The analysis found that Rosenbergiella_YN46 bacteria had a high colonization rate in the mosquito gut in Wenshan and Pu'er (non-dengue-endemic areas), while a low proportion in the mosquito gut in Xishuangbanna and Lincang (dengue-endemic areas) was low. These results indicated that the distribution and colonization of Rosenbergiella_YN46 bacteria was highly correlated with the specificity of dengue-endemic areas in Yunnan Province.
The distribution of Rosenbergiella_YN46 in nature was highly negatively correlated with the specificity of dengue endemic areas in Yunnan Province
In order to bring these findings to practical application, the research team designed and executed a series of field intervention experiments. By adding Rosenbergiella_YN46 bacteria to mosquito breeding waters, the researchers succeeded in colonizing the commensal bacteria into the mosquitoes' gut and significantly reducing the proportion of mosquitoes infected with dengue virus. These experiments not only verified the effectiveness of Rosenbergiella_YN46 bacteria in blocking the transmission of viruses by mosquitoes, but also demonstrated the potential application value of this method.
In addition, the study also focused on the safety of Rosenbergiella_YN46 bacteria, confirming that the symbiotic relationship between this symbiotic bacteria and mosquitoes has been stable in nature, and its environmental intervention strategies will not affect the natural adaptability of mosquitoes or develop antimicrobial resistance problems. Therefore, environmental intervention with Rosenbergiella_YN46 can be used as a control strategy with great application potential, and the most suitable natural plant source of the bacterium can be further confirmed in the future, and it is expected that the intervention of dengue virus transmission can be realized through the sowing of natural plants to block the spread of mosquito-borne virus infectious diseases in nature. However, the diverse natural habitats and complex intestinal microbiota of mosquitoes pose significant challenges to the colonization efficiency and effectiveness of Rosenbergiella_YN46, and the effectiveness of Rosenbergiella_YN46 colonization in mosquito gut still needs to be further studied in the natural environment.