As summer approaches, the pesky mosquitoes are gearing up for action.
But don't underestimate these bloodsuckers. They don't just leave an itchy bump behind; they also carry viruses from one victim to another, causing infectious diseases.
On April 19th, a team led by Professor Cheng Gong from the School of Basic Medical Sciences at Tsinghua University, along with collaborators, proposed a novel strategy to halt the spread of infectious diseases by mosquitoes. They discovered a crucial symbiotic bacterium in Yunnan, China, which, when intervened in its environment, effectively disrupts the mosquitoes' ability to carry and transmit viruses in epidemic regions. Their findings were published in the journal Science.
The research team is discussing, with Cheng Gong in the second from the left. Interviewee supplied photo (same below).
Which mosquitoes are susceptible to viruses? Focus on their gut symbiotic bacteria
The spread of mosquito-borne viral infections is a significant threat to human health and life.
Among them, dengue fever and Zika fever are the most representative mosquito-borne viral infections. Dengue fever is prevalent in more than 100 countries globally, infecting up to 390 million people annually, with 500,000 to 1 million hospitalized. In China, Yunnan Province is the main area where severe mosquito-borne viral infections like dengue fever are prevalent.
Zika fever, on the other hand, erupted suddenly in the Pacific Islands and South America from 2015 to 2017, infecting over 223,000 cases within a year, with thousands of cases of microcephaly in newborns. The World Health Organization declared it an international public health emergency.
"So far, most mosquito-borne viruses have no effective drugs or vaccines. People rely on the large-scale use of insecticides to kill mosquitoes, which not only harms human health and the ecological environment but also cannot control the spread of mosquito-borne viruses. Because mosquitoes quickly develop resistance, rendering insecticides ineffective," said Cheng Gong, the corresponding author of the paper, to China Science Daily. He emphasized the urgent need for cost-effective, environmentally friendly prevention and control strategies to halt the widespread transmission of mosquito-borne viruses.
Cheng Gong's team has always been concerned about the regulatory relationship between mosquito gut microbiota and mosquito-borne viruses. In the transmission cycle of mosquito-borne viruses, mosquitoes first feed on blood from infected individuals carrying the virus. Subsequently, the virus infects mosquito gut cells and spreads throughout the mosquito's body, eventually infecting the mosquito's salivary glands, enabling the mosquito to transmit the virus.
"Since the mosquito gut tissue is the first organ to be infected, the microbiota in the mosquito gut must have complex interactions with the virus, determining the mosquito's susceptibility to the virus," Cheng Gong stated, which has become a consensus in the academic community.
Starting from the gut symbiotic bacteria of mosquitoes, researchers discovered a "helper" for viruses in the laboratory-reared population of Egyptian mosquitoes—the sticky sandfly bacterium, which can assist in infecting mosquito gut epithelial cells, increasing the mosquito's susceptibility to the virus.
Locking in bacteria from thousands of mosquitoes in the wild
In the laboratory, does the gut symbiotic bacteria that affect mosquito susceptibility to viruses also exist in the natural environment? Can mosquito carriage and virus transmission be disrupted by regulating symbiotic bacteria?
In fact, there is a huge difference between the natural environment and the laboratory environment. In the natural world, the composition and abundance of gut microbiota in wild mosquitoes are greatly influenced by their living environment, some coming from environmental microorganisms in breeding water bodies, and others from symbiotic microorganisms in environmental plant sap and nectar. The composition of environmental microorganisms varies greatly in different regions, leading to significant differences in the ability of mosquitoes to carry and transmit viruses.
Therefore, researchers decided to conduct in-depth field research.
Since 2020, over three years, researchers have captured thousands of wild female mosquitoes in border areas of Yunnan Province. "We isolated and cultured 55 strains of mosquito gut symbiotic bacteria from them, mixed them with human blood and viruses, and fed them to mosquitoes to see if there are any symbiotic bacteria that can prevent mosquitoes from carrying viruses," Cheng Gong explained.
The study showed that in the gut of Aedes albopictus and Aedes aegypti mosquitoes, settling a bacterium of the Rosenbergiella genus, named Rosenberg_YN46, can significantly inhibit mosquitoes from being infected with dengue virus and Zika virus through blood-feeding.
Rosenberg bacteria are associated with plant sap and nectar and are widely present in nature. They rapidly acidify the mosquito gut environment (pH≈6.0) by secreting a glucose dehydrogenase, reshaping the mosquito gut microenvironment.
Previous studies have shown that the envelope protein of dengue virus and other mosquito-borne viruses is sensitive to acidic signals. When the virus is in an acidic environment with a pH value lower than 6.5, the envelope protein undergoes irreversible conformational changes, causing the virus particles to enter a disassembled state and lose infectivity.
"Therefore, the acidification of the gut environment can directly inactivate virus particles entering the gut, thereby inhibiting mosquitoes' ability to acquire viruses through blood-feeding, significantly reducing their susceptibility to viruses," Cheng Gong explained.
Experimental Greenhouses in Yunnan
Environmental Intervention in Epidemic Areas
To verify experimental results, researchers hope to further investigate whether the prevalence of dengue fever in Yunnan is correlated with the natural distribution of Rosenburg_YN46 bacteria in the environment.
It is understood that under similar climatic conditions and mosquito population densities, there are significant differences in the prevalence of dengue fever in different regions of Yunnan, with clear hotspots.
"According to epidemiological survey records over the past decade, we found that dengue fever outbreaks are persistent in Xishuangbanna and Lincang, while neighboring Wenshan and Pu'er have almost no local cases of dengue fever," said Cheng Gong.
Therefore, they conducted in-depth investigations in these four areas, collecting mosquitoes from locations with similar climate and environmental factors, and detecting the colonization of Rosenburg_YN46 bacteria in the guts of wild mosquitoes.
Analysis revealed that Rosenburg_YN46 bacteria had a high colonization rate in the guts of mosquitoes in Wenshan and Pu'er, the two non-dengue fever epidemic areas, while its colonization rate was low in Xishuangbanna and Lincang.
So, can environmental intervention with Rosenburg_YN46 bacteria be carried out in the water bodies of the two epidemic areas to naturally colonize wild mosquitoes?
"Around this question, we intervened with Rosenburg_YN46 bacteria in laboratory water bodies, followed by hatching wild Aedes albopictus eggs obtained from Xishuangbanna in this water body, and then detected the colonization of this symbiotic bacteria in the guts of hatched larvae, pupae, and adults," Cheng Gong explained.
The results showed that Rosenburg_YN46 bacteria could be efficiently colonized in the guts of hatched mosquitoes through environmental water intervention. At the same time, mosquitoes hatched in the intervened water environment were less susceptible to virus infection.
Subsequently, researchers conducted field intervention experiments in Mengla County, Xishuangbanna Dai Autonomous Prefecture. They intervened with Rosenburg_YN46 bacteria in local breeding water bodies and hatched local mosquitoes using the local water and soil environment. The results showed a significant decrease in the proportion of mosquitoes hatching with dengue virus infection.
The Experimental Greenhouse in Yunnan
A Safe and Reliable Mosquito Control Strategy
In the ongoing battle against mosquito-borne viral infections, safety is a paramount concern. The Rosenberger YN46 fungus used in this study is a naturally occurring symbiotic organism, with a stable symbiotic relationship with mosquitoes in the natural environment.
As such, Cheng Gong asserts that implementing the Rosenberger YN46 fungus environmental intervention strategy selectively suppresses mosquito-borne virus transmission without inducing resistance in mosquitoes or affecting their ecological adaptability in the wild. This makes it a safe and reliable approach. "It holds tremendous potential as a control strategy, effectively halting the spread of mosquito-borne viral infections in the natural environment," says Cheng Gong.
"This research, from an environmental ecology perspective, explores and addresses the patterns of transmission and spread of mosquito-borne viral infections. By intervening in the environment with symbiotic fungi, it achieves the interruption of virus transmission carried by mosquitoes in the wild. This will lay a new theoretical framework and application strategy for the prevention and control of mosquito-borne infectious diseases," comments Kang Le, academician of the Chinese Academy of Sciences and researcher at the Institute of Zoology, Chinese Academy of Sciences.
Gao Fu, academician of the Chinese Academy of Sciences and researcher at the Institute of Microbiology, Chinese Academy of Sciences, believes, "This research has identified an environmental biological factor that determines the transmission of mosquito-borne viruses, providing a new technological platform and theoretical basis for the prevention and control of mosquito-borne viral infections based on the 'One Health' concept."
Related Paper Information: Link to the Paper
