Quorum sensing-activated phenylalanine metabolism drives OMV biogenesis to enhance mosquito commensal colonization resistance to Plasmodium.

Gut microbiota and its symbiotic relationship with the host are crucial for preventing pathogen infection. However, little is known about the mechanisms that drive commensal colonization. Serratia bacteria, commonly found in Anopheles mosquitoes, potentially mediate mosquito resistance to Plasmodium. Using S. ureilytica Su_YN1 as a model, we show that a quorum sensing (QS) circuit is crucial for stable colonization. After blood ingestion, the QS synthase SueI generates the signaling molecule N-hexanoyl-L-homoserine lactone (C6-HSL). Once C6-HSL binds to the QS receptor SueR, repression of the phenylalanine-to-acetyl-coenzyme A (CoA) conversion pathway is lifted. This pathway regulates outer membrane vesicle (OMV) biogenesis and promotes Serratia biofilm-like aggregate formation, facilitating gut adaptation and colonization. Notably, exposing Serratia Su_YN1-carrying Anopheles mosquitoes to C6-HSL increases Serratia gut colonization and enhances Plasmodium transmission-blocking efficacy. These findings provide insights into OMV biogenesis and commensal gut colonization and identify a powerful strategy for enhancing commensal resistance to pathogens.

Outer membrane vesicles from a mosquito commensal mediate targeted killing of Plasmodium parasites via the phosphatidylcholine scavenging pathway.

The gut microbiota is a crucial modulator of Plasmodium infection in mosquitoes, including the production of anti-Plasmodium effector proteins. But how the commensal-derived effectors are translocated into Plasmodium parasites remains obscure. Here we show that a natural Plasmodium blocking symbiotic bacterium Serratia ureilytica Su_YN1 delivers the effector lipase AmLip to Plasmodium parasites via outer membrane vesicles (OMVs). After a blood meal, host serum strongly induces Su_YN1 to release OMVs and the antimalarial effector protein AmLip into the mosquito gut. AmLip is first secreted into the extracellular space via the T1SS and then preferentially loaded on the OMVs that selectively target the malaria parasite, leading to targeted killing of the parasites. Notably, these serum-induced OMVs incorporate certain serum-derived lipids, such as phosphatidylcholine, which is critical for OMV uptake by Plasmodium via the phosphatidylcholine scavenging pathway. These findings reveal that this gut symbiotic bacterium evolved to deliver secreted effector molecules in the form of extracellular vesicles to selectively attack parasites and render mosquitoes refractory to Plasmodium infection. The discovery of the role of gut commensal-derived OMVs as carriers in cross-kingdom communication between mosquito microbiota and Plasmodium parasites offers a potential innovative strategy for blocking malaria transmission.

A natural symbiotic bacterium drives mosquito refractoriness to Plasmodium infection via secretion of an antimalarial lipase.

The stalling global progress in the fight against malaria prompts the urgent need to develop new intervention strategies. Whilst engineered symbiotic bacteria have been shown to confer mosquito resistance to parasite infection, a major challenge for field implementation is to address regulatory concerns. Here, we report the identification of a Plasmodium-blocking symbiotic bacterium, Serratia ureilytica Su_YN1, isolated from the midgut of wild Anopheles sinensis in China that inhibits malaria parasites via secretion of an antimalarial lipase. Analysis of Plasmodium vivax epidemic data indicates that local malaria cases in Tengchong (Yunnan province, China) are significantly lower than imported cases and importantly, that the local vector A. sinensis is more resistant to infection by P. vivax than A. sinensis from other regions. Analysis of the gut symbiotic bacteria of mosquitoes from Yunnan province led to the identification of S. ureilytica Su_YN1. This bacterium renders mosquitoes resistant to infection by the human parasite Plasmodium falciparum or the rodent parasite Plasmodium berghei via secretion of a lipase that selectively kills parasites at various stages. Importantly, Su_YN1 rapidly disseminates through mosquito populations by vertical and horizontal transmission, providing a potential tool for blocking malaria transmission in the field.

Genomic landscape and genetic manipulation of the black soldier fly Hermetia illucens, a natural waste recycler.

The black soldier fly (BSF), Hermetia illucens (Diptera: Stratiomyidae), is renowned for its bioconversion of organic waste into a sustainable source of animal feed. We report a high-quality genome of 1.1 Gb and a consensus set of 16,770 gene models for this beneficial species. Compared to those of other dipteran species, the BSF genome has undergone a substantial expansion in functional modules related to septic adaptation, including immune system factors, olfactory receptors, and cytochrome P450s. We further profiled midgut transcriptomes and associated microbiomes of BSF larvae fed with representative types of organic waste. We find that the pathways related to digestive system and fighting infection are commonly enriched and that Firmicutes bacteria dominate the microbial community in BSF across all diets. To extend its potential practical applications, we further developed an efficient CRISPR/Cas9-based gene editing approach and implemented this to yield flightless and enhanced feeding capacity phenotypes, both of which could expand BSF production capabilities. Our study provides valuable genomic and technical resources for optimizing BSF lines for industrialization.