• Engineered Bacteria Combat Concurrent Malaria and Arbovirus Transmission (March 2025)

  • Mar 2 2025
  • Duración: 22 m
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Engineered Bacteria Combat Concurrent Malaria and Arbovirus Transmission (March 2025)

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  • Briefing Document: Engineered Symbionts for Concurrent Malaria and Arbovirus Transmission ControlCitation: Hu, W., Gao, H., Cui, C. et al. Harnessing engineered symbionts to combat concurrent malaria and arboviruses transmission. Nat Commun 16, 2104 (2025). https://doi.org/10.1038/s41467-025-57343-2Dates: Received - 27 July 2024 | Accepted - 19 February 2025 | Published - 01 March 2025Prepared for: Saleh LabExecutive Summary:This research presents a novel paratransgenesis strategy utilizing engineered symbiotic bacteria (Serratia AS1) in mosquitoes to simultaneously combat the transmission of malaria parasites (transmitted by Anopheles mosquitoes) and arboviruses like dengue and Zika (transmitted by Aedes mosquitoes). The study demonstrates the successful engineering of Serratia AS1 to express anti-Plasmodium and anti-arbovirus effector proteins under the control of a blood-induced promoter. Both laboratory and semi-natural field-cage experiments show that these engineered bacteria effectively spread through mosquito populations and significantly inhibit pathogen infections in both Anopheles and Aedes mosquitoes, including reducing co-infection rates of dengue and Zika viruses. This work lays the groundwork for a promising tool to address the growing challenge of concurrent mosquito-borne disease outbreaks.Main Themes and Important Ideas/Facts:The Growing Threat of Concurrent Mosquito-Borne Diseases:More than half of the global population lives in areas at risk of contracting two or more major mosquito-borne diseases.The geographic distributions of Anopheles (malaria) and Aedes (arboviruses) mosquitoes are increasingly overlapping, leading to co-existence and potential co-infection scenarios.Co-infections of malaria and arboviruses (dengue, Zika, chikungunya) have been reported in various regions.Co-circulation and simultaneous co-infection of multiple arboviruses are also prevalent.These concurrent infections pose complex challenges for disease surveillance, diagnosis, and treatment."The overlapping distributions highlight the inevitable co-existence and potential co-infection of malaria and arboviruses, or multiple arboviruses, in single host. Such scenarios pose complex and multifaceted public health challenges."Limitations of Current Mosquito Control Strategies:Reliance on mosquito management is hampered by widespread insecticide resistance.Behavioral changes in Anopheles mosquitoes (e.g., outdoor biting) and antimalarial drug resistance have stalled progress in malaria control.Current global outbreaks highlight the inadequacies of existing control tools."This situation underscores the urgent need for innovative intervention strategies to tackle the concurrent transmission of malaria and arbovirus diseases."Paratransgenesis as a Promising Innovative Strategy:Paratransgenesis, utilizing genetically manipulated symbionts to inhibit pathogens, is an attractive approach.While promising for malaria, its effectiveness against arboviruses and its potential to simultaneously target both requires further exploration."Here, we explore the potential of parastransgenesis strategy to concurrently inhibit the transmission of Plasmodium and arboviruses by Anopheles and Aedes mosquitoes, respectively."Identification and Engineering of Serratia AS1 as a Multifunctional Symbiont:The symbiotic bacterium Serratia AS1 efficiently spreads through both Anopheles and Aedes mosquito populations (horizontally and vertically).Laboratory cage experiments confirmed efficient spread in An. stephensi and Ae. aegypti.Serratia AS1 proliferates in the mosquito midgut after a blood meal without significant fitness costs to the mosquitoes.Wild-type Serratia AS1 did not significantly affect dengue virus infection in Ae. aegypti, making it a suitable chassis for engineering."...indicating that Serratia AS1 can efficiently spread throughout these two mosquito populations.""...without causing obvious negative impact on fitness costs in both the mosquito species..."Development of Engineered Serratia AS1 Strains Expressing Anti-Pathogen Effectors:The study engineered Serratia AS1 to co-express anti-Plasmodium peptides (Shiva1, scorpine) and anti-arbovirus peptides (DN59, Z2) using the efficient HlyA secretion system.The initial construct (AS1-DK) with constitutive expression (using pnptII promoter) showed strong inhibition of P. berghei in Anopheles and DENV2 in Aedes."We found that AS1-DK strongly inhibited P. berghei ANKA (Pb ANKA) development in An. stephensi mosquitoes...and DENV2 infection in Ae. aegypti mosquitoes."Importance and Identification of a Blood-Induced Promoter (LipA):Constitutive expression of effectors can impose fitness burdens on bacteria and potentially affect mosquitoes or lead to resistance.Blood-inducible promoters are advantageous as effector expression is activated only upon blood meal ingestion, coinciding with pathogen entry.A comprehensive analysis of Serratia transcriptional and proteomic data identified ...
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