The discovery of a naturally occurring symbiotic bacterium that inhibits the transmission of flaviviruses by Aedes mosquitoes, presents a promising avenue for the safe and efficient biocontrol of these pathogens.

Mosquito-borne flaviviral diseases such as dengue represent significant public health challenges, exacerbated by the absence of widely accessible pharmaceutical treatments or vaccines. Existing methods of mosquito control have demonstrated limited efficacy in blocking viral transmission. There is thus an urgent need for cost-effective and environmentally sustainable strategies to control the transmission of these viruses.

Researchers have identified a pivotal symbiotic bacterium within the environment of Yunnan Province, China, which affects mosquito susceptibility to flaviviruses. Field trials conducted in Xishuangbanna demonstrate that manipulation of this bacterium can successfully inhibit dengue virus transmission.

This breakthrough discovery presents a pioneering approach to addressing significant mosquito-borne diseases, elucidated by Cheng Gong, the lead author of a recent publication in the journal Science, in April 2024.

Harnessing Bacterial Potential

Researchers have long explored the impact of mosquito gut microbes on virus transmission, identifying their functions in laboratory settings.

However, a substantial disparity exists between controlled settings and natural habitats. In the wild, the composition and abundance of mosquito gut microbes are profoundly shaped by their environmental milieu. This raises the pivotal inquiry: Are there commensal bacteria within natural ecosystems that efficaciously modulate mosquitoes' viral transmission capacities in field regions?

Since 2020, researchers have conducted fieldwork in the border regions of China's Yunnan Province, gathering thousands of Aedes mosquitoes and isolating their gut symbiotic bacteria for functional screening. Their study revealed that colonization of Aedes mosquito intestines with Rosenbergiella sp. YN46 (Rosenbergiella_YN46) significantly hindered mosquito infection with flaviviruses during blood-feeding, suggesting its crucial role as a determinant of viral infectivity.

This commensal bacterium swiftly acidifies the mosquito's intestinal environment (pH ≈ 6.0) via glucose dehydrogenase secretion (RyGDH), leading to intestinal microenvironment remodeling. Previous research has established that envelope proteins of flaviviruses, like dengue, are sensitive to acidic conditions. In an acidic environment (pH<6.5), these proteins irreversibly deform, rendering viral particles inactive. Consequently, the acidified gut environment directly deactivates virus particles, impeding their acquisition by mosquitoes during blood meals and drastically reducing mosquito susceptibility to viruses.

Rosenbergiella_YN46 bacteria block viral transmission by remodeling the mosquito gut microenvironment via the secretion of RyGDH.

Rosenbergiella_YN46 in Field isolates

Yunnan Province, a major hotspot for virulent mosquito-borne infections like dengue fever, exhibits significant heterogeneity in epidemic hotspots across different areas. Over the past decade, Xishuangbanna and Lincang have experienced perennial outbreaks, whereas neighboring Wenshan and Puer report few local epidemics.

Researchers collected mosquitoes from these four areas with similar environmental factors and analyzed Rosenbergiella_YN46 colonization in their guts. Results revealed a high colonization rate of Rosenbergiella_YN46 in Wenshan and Puer (low dengue-incidence areas) and a low colonization rate in Xishuangbanna and Lincang (high dengue-incidence regions). This correlation suggests that the distribution and colonization of Rosenbergiella_YN46 are closely linked to the dengue-endemic regions in Yunnan.

The presence of Rosenbergiella_YN46 in nature exhibits a strong correlation with the area specificity of dengue fever low-incidence regions in Yunnan.

Semi-field intervention

Researchers conducted a semi-field investigation to evaluate the efficacy of disrupting Rosenbergiella_YN46 within the environment of a region with high dengue incidence in blocking the transmission of dengue virus by local mosquitoes. Xishuangbanna (21°31′8.77″N, 101°36′22.89″E) was selected as the study site, where a controlled mosquito habitat was established utilizing local soil and water. Subsequently, a bacterial intervention involving Rosenbergiella_YN46 was introduced into the breeding water to monitor the infection rate of dengue virus among the hatched mosquitoes.

Results revealed a notable decrease in the infection ratio of dengue virus among hatched mosquitoes originating from high dengue-incidence areas subsequent to the implementation of Rosenbergiella_YN46 intervention within the mosquitoes breeding site. This suggests that Rosenbergiella_YN46 intervention in the environment effectively inhibits mosquitoes’ ability to infect and transmit viruses in high dengue-incidence areas, offering a novel technical platform and approach for combating dengue fever.

Rosenbergiella_YN46 interventions in breeding sites effectively reduce the transmission of dengue virus by newly emerged adult mosquitoes.

“Indeed, Rosenbergiella_YN46, an indigenous symbiotic bacterium found in the environment, has established a stable symbiosis with mosquitoes in their native habitats. Implementing an environmental intervention using Rosenbergiella_YN46 to block mosquito-borne viral transmission represents an eco-friendly biocontrol strategy. This intervention approach holds great promise for controlling mosquito-borne viral transmission in the endemic regions,” says Gong Cheng, a microbiology scientist at Tsinghua University.

Reference

Zhang et al. A naturally isolated symbiotic bacterium suppresses flavivirus transmission by Aedes mosquitoes. Science (2024). DOI: 10.1126/science.adn9524

Editor: Li Han