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At first glance, does it seem like the people in the picture are camping? In fact, this is the "mosquito greenhouse" built by Professor Cheng Gong from Tsinghua University and doctoral student Zhang Liming in Yunnan. By studying mosquitoes, they published a paper in Science.

In the study, they first discovered and reported a new environment-derived Aedes mosquito intestinal symbiotic bacterium, Rosenbergiella sp. YN46, and proved that it can reduce the mosquitoes' susceptibility to dengue and Zika viruses.

This achievement indicates that Rosenbergiella sp. YN46 is an environmental symbiotic bacterium naturally carried by Aedes mosquitoes, which can specifically reduce the mosquitoes' susceptibility to viruses, is not easy to produce mosquito drug resistance, and has no potential harm to the environment and mammalian hosts.

Undoubtedly, this study can provide new ideas for the biological prevention of mosquito-borne viral infectious diseases based on environmental symbiotic bacteria intervention.

The research group also put forward a strategy for environmental intervention to block the transmission of mosquito-borne viruses based on the "One-health" concept, thus providing a new perspective for the prevention and treatment of severe mosquito-borne viruses such as dengue fever.Bacteria Discovered That Can Reduce Mosquitoes' Susceptibility to Dengue and Zika Viruses

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In recent years, a variety of emerging and re-emerging mosquito-borne viral diseases have posed a serious threat to human health and public health safety. Taking dengue fever and Zika fever as examples, dengue fever has infected more than 390 million people worldwide, with 500,000 to 1 million people requiring hospital treatment each year.

Zika fever, on the other hand, triggered a large-scale outbreak in the Pacific Islands and South America between 2015 and 2017, with more than 223,000 confirmed cases, accompanied by thousands of cases of microcephaly in newborns. As a result, the international health organization declared the Zika outbreak a public health emergency of international concern.

However, for most mosquito-borne viruses, there are still no effective drugs and vaccines, and traditional mosquito control measures cannot completely control the spread of these viruses. Therefore, people urgently need a safe and effective new strategy to interrupt the widespread transmission of mosquito-borne viruses.Previously, Cheng Gong and his team discovered that the microorganisms in the mosquito gut play an important role in determining their ability to transmit vector-borne viruses.

These gut microorganisms are partly derived from environmental microorganisms in the water where mosquitoes breed, and another part comes from symbiotic microorganisms in plant sap or nectar from the environment.

Therefore, even within the same species of mosquitoes, there is a significant difference in the composition of gut microorganisms due to differences in the growth environment.

Although Yunnan Province is a major epidemic area for severe mosquito-borne viral infectious diseases such as dengue fever in China, the distribution of dengue fever outbreaks in different areas of Yunnan Province still shows uneven and hotspot characteristics even under similar climatic conditions and mosquito population densities.

Therefore, an important question is: In the natural environment, is there a gut symbiotic bacterium that determines the ability of mosquitoes to infect and transmit viruses in the natural environment? Is this uneven geographical distribution of dengue fever outbreaks related to the differences in the gut microorganisms of mosquitoes?To answer the above questions and explore new strategies for blocking the transmission of mosquito-borne viruses based on gut symbionts, the research team carried out a series of in-depth studies.

From Beijing to Yunnan to "Raise Mosquitoes"

It is understood that there are not many papers of this kind that can be published in the Science journal. So, how did Cheng Gong's research team carry out this study?

He said: "This study began with our preliminary exploration of mosquito gut symbionts. We found in the laboratory-reared Aedes aegypti population that Serratia marcescens can assist in virus infection of mosquito gut epithelial cells, enhancing the mosquitoes' susceptibility to the virus."However, the team realized that there is a huge difference between the laboratory environment and the natural world. To understand the impact of mosquito gut microbiota on viral infection in nature, answers need to be sought from the natural environment.

In 2020, after establishing contact with Researcher Wang Jinglin from the Yunnan Provincial Academy of Animal Husbandry and Veterinary Science, the Cheng Gong research group relied on the institute to establish the Cheng Gong Expert Workstation in Yunnan Province, which provided an opportunity to study the interaction between vector mosquitoes, mosquito-borne viruses, and symbiotic microorganisms in the field.

Based on the expert workstation in Yunnan, the Cheng Gong team began to explore the relationship between mosquito gut symbiotic bacteria and viral infection transmission in the natural environment.

Since 2020, the research group has gone deep into the border areas of Yunnan Province, collected thousands of wild female mosquitoes, and isolated 55 strains of mosquito gut symbiotic bacteria for functional screening.

The research found that a symbiotic bacterium named Rosenbergiella sp. YN46 is established in the gut of Aedes albopictus, which can significantly inhibit the mosquito's infection with dengue virus and Zika virus.Mechanism research indicates: Rosenbergiella sp. YN46 secretes glucose dehydrogenase, which rapidly acidifies the intestinal environment of mosquitoes, leading to irreversible conformational changes of the viral envelope protein in an acidic environment with pH < 6.5, thereby losing infectious activity.

To further explore the relationship between Rosenbergiella sp. YN46 and the prevalence of dengue fever, the team collaborated with Associate Researcher Wang Daxin from the BGI Life Sciences Research Institute.

Through this, they analyzed the distribution of Rosenbergiella sp. YN46 in different areas of Yunnan Province and compared it with the correlation of dengue fever prevalence.

The results show that Rosenbergiella sp. YN46 has a higher colonization rate in the intestines of mosquitoes in Wenshan and Puer (non-dengue fever epidemic areas), while it is lower in Xishuangbanna and Lincang (dengue fever epidemic areas).

To evaluate the application value of Rosenbergiella sp. YN46 in the prevention and control of dengue fever, the research group conducted field experiments in Xishuangbanna Prefecture, Yunnan Province.The results showed that by adding Rosenbergiella sp. YN46 to mosquito breeding water bodies, the proportion of mosquitoes infected with dengue virus in the population could be reduced.

Cheng Gong said: "This result can provide important experimental evidence for Rosenbergiella sp. YN46 to block the transmission of viruses by mosquitoes in the natural environment."

In summary, the team revealed the potential role of Rosenbergiella sp. YN46 as a symbiotic bacterium in mosquito intestines in blocking the transmission of mosquito-borne viruses through platform construction, core question raising, laboratory research and demonstration, and the implementation of field interventions.

"Mosquito greenhouse" and the story of local villagersIt is also reported that, in order to verify the potential of Rosenbergiella sp. YN46 in dengue fever prevention and control, the research team conducted semi-field intervention studies in Mengla County, Yunnan Province.

This is a brand-new attempt by the team, which can provide important evidence for whether Rosenbergiella sp. YN46 has the application potential in dengue fever prevention and control.

After a series of surveys and site selections, they chose a certain area in Mengla County, Yunnan Province (21°31'8.77"N, 101°36'22.89"E) as the field intervention point.

After some efforts, they finally completed the construction of the "mosquito greenhouse". However, during the first experiment, an unexpected event occurred, and the local Dai compatriots sprayed pesticides, causing the death of mosquito larvae.

After communicating with the local villagers and explaining their research intentions and potential benefits for dengue fever control, the team cleaned the land again and added new water, mosquito eggs, and Rosenbergiella sp. YN46 to the greenhouse.During this period, they also encountered the problem of frogs preying on mosquito larvae. To prevent the invasion of frogs, they set up a more stringent barrier and checked the experimental environment every day.

After continuous adjustments and corrections, the experiment finally made progress.

The final research data showed that the water intervention of Rosenbergiella sp. YN46 could enable the efficient colonization of Aedes albopictus in areas where dengue fever is prevalent with Rosenbergiella sp. YN46.

More importantly, Aedes albopictus carrying this symbiotic bacterium had a strong resistance to the dengue virus, effectively blocking the transmission cycle of the dengue virus.

Recently, the related paper was published in Science with the title "A naturally isolated symbiotic bacterium suppresses flavivirus transmission by Aedes mosquitoes" [1].Tsinghua University PhD student Li-Ming Zhang is the first author, and Gong Cheng serves as the corresponding author.

The reviewers unanimously believe that this study is of great significance for the prevention and control of severe mosquito-borne viruses such as dengue fever, and the dengue fever intervention strategy based on Rosenbergiella sp. YN46 has a good prospect for transformation.

One of the reviewers commented that the study reported a new intestinal symbiotic bacterium of the Aedes albopictus mosquito, which can reduce the susceptibility of Aedes albopictus and the main dengue fever vector, Aedes aegypti, to dengue fever.

Importantly, the quantity of this bacterium exerting antiviral effects is within the natural range.

This reviewer also stated: It is impressive that the study not only reported the preliminary discovery of this antiviral effect but also convincingly demonstrated its mechanism of action, and then conducted a semi-field test to prove its potential in the control of dengue fever.The continued commentary states: The research data in this study has achieved positive results, and the conclusions are fully consistent with the data.

These are highly influential results, and the prospect of translating them into practical dengue control seems very high, especially considering that it is a bacterium naturally present in the intestines of the dengue vector - the Aedes mosquito, which can be used for non-genetically modified biological control.

Another reviewer pointed out that the colonization rate of Rosenbergiella is significantly higher than that of mosquitoes in dengue-endemic areas, which also confirms the effectiveness of the experimental results.

In summary, these conclusions are fully supported by a series of extensive experiments, including gene-knockout bacteria.

As mentioned earlier, in the natural environment, the intestinal microbiota composition of mosquitoes is very diverse. Therefore, the research team plans to carry out specific dengue intervention applications in the following two directions:Firstly, in areas at high risk of dengue fever, the team plans to increase the proportion of Aedes mosquitoes that can colonize with Rosenbergiella sp. YN46 in the water environment of mosquito breeding sites, by introducing the bacteria Rosenbergiella sp. YN46, thereby reducing the virus susceptibility of Aedes mosquitoes and blocking the spread of the virus.

Secondly, bacteria of the genus Rosenbergiella are currently known to have a close relationship with plant-derived sap and nectar, and they are ubiquitous environmental symbionts in the natural environment.

Therefore, the research group will carry out the environmental plant traceability of Rosenbergiella sp. YN46, identifying the plant host of Rosenbergiella sp. YN46.

In experimental research, they will also mainly focus on two aspects:

Firstly, the research group will delve into the environmental origins of Rosenbergiella sp. YN46 to better understand its ecological significance in the natural environment, thereby providing a scientific basis for vector-borne virus biological control strategies based on environmental intervention.Considering the origin of mosquito gut microbes, they plan to go to the original site of mosquito collection in Wenshan Prefecture, Yunnan Province, to collect local plant sap, nectar, and water and soil from breeding sites, and then detect the environmental source of Rosenbergiella sp. YN46 through deep sequencing.

This is expected to help determine the natural distribution of the bacteria and further understand its role in the natural environment.

Secondly, the team will cooperate with Kunming Customs, Yunnan International Health Travel Care Center, Kunming Medical University, Yunnan Provincial Institute of Parasitic Diseases Prevention and Control, and other units to carry out an environmental intervention pilot of Rosenbergiella sp. YN46 in Mengla County, Xishuangbanna Prefecture, Yunnan Province.

"We will add the Rosenbergiella sp. YN46 bacteria to mosquito traps to attract mosquitoes to lay eggs, assess the carrying rate of local mosquitoes for Rosenbergiella sp. YN46, and detect its impact on Dengue virus infection," said Cheng Gong.

He stated that this pilot aims to verify the intervention effect of Rosenbergiella sp. YN46 in real natural habitats and evaluate its safety, applicability, and effectiveness in different geographical and ecological environments.Through this, they hope to delve deeper into the potential applications of Rosenbergiella sp. YN46, providing new scientific evidence for the prevention and control of mosquito-borne viruses.

At the same time, they will also be based on the "One-Health" concept, by planting a large number of such plants in areas where dengue fever is prevalent, which will significantly increase the proportion of Aedes mosquitoes carrying Rosenbergiella sp. YN46, reducing the virus susceptibility of the vector mosquitoes, and interrupting the virus transmission.

It is expected that this strategy will not only be highly targeted but also will not have a negative impact on the ecosystem. Therefore, it is expected to become an environmentally friendly measure for the prevention and control of dengue fever in high-risk areas.