Schirra, H. J. | Search bioRxiv

bioRxiv2025

Wolbachia-mediated antiviral protection is driven by its multimodal effects on Drosophila melanogaster metabolism

Wolbachia, a common endosymbiont of Drosophila melanogaster, provides a profound antiviral effect in insects. Wolbachia-mediated viral interference has been employed to limit the spread of arboviruses, including dengue. However, the mechanisms underpinning Wolbachia-mediated viral interference are not consistently understood. Previous studies have identified resource competition as a potential mechanism by which Wolbachia disrupts viral replication. Our study uses nuclear magnetic resonance (NMR)-based metabolomics to characterize the bi- and tripartite host-Wolbachia-virus interactions using the model insect Drosophila melanogaster, the protective Wolbachia strain wMel and the pathogenic Drosophila C virus (DCV). The findings reveal that wMel-infected flies showed increased simple carbohydrate catabolism relative to uninfected Drosophila. DCV infection perturbed nucleotide synthesis and nucleotide abundance in Drosophila compared to uninfected Drosophila, driving metabolism to likely meet the viral replication demands imposed on the host. Notably, co-infected Drosophila exhibited a metabolic profile more similar to wMel-infected flies than DCV-infected flies, suggesting that wMel drives metabolism in a direction that at least temporarily inhibits DCV replication. The metabolic profile is indicative of a hypoxic environment that has been known to trigger immune pathways that further contribute to Wolbachia-mediated pathogen blocking. It is probable that Wolbachia-mediated antiviral protection is a multimodal consequence of wMels influence on host metabolism, rather than a single mechanism. These findings will guide future research and contribute to the continued success of Wolbachia-based vector control strategies against RNA arboviruses, potentially leading to novel approaches for defending against such pathogens and improving vector control strategies. Significance StatementWolbachia-mediated antiviral protection has been used extensively to control the spread of insect-borne viruses, with the release of Wolbachia-infected mosquitoes eradicating local dengue transmission in some regions. Despite this real-world impact, how Wolbachia disrupted viruses remained unclear, with three common mechanisms predicted: (1) competition between Wolbachia and virus for host metabolites, or stimulation of host antiviral pathways via (2) immune priming and/or (3) the RNA interference pathway. Our findings reveal that in Drosophila melanogaster, Wolbachia does compete for some metabolites, but it exerts a greater effect by altering host metabolism which in turn creates an intracellular environment unfavorable for viral replication and indirectly triggers an immune response. Thus, the mechanism by which Wolbachia disrupts viruses relies on both metabolic and immune pathways. Understanding these metabolic mechanisms is crucial for optimizing and sustaining this vector control strategy and for shaping future efforts to combat vector-borne diseases.

systems biology↗

bioRxiv2025

New glucose-abstaining Chlorella algae doubles mammalian cell culture longevity, boosts performance and drops serum needs enabling scaled applications.

Mammalian cell culture technologies are crucial for recombinant protein production, organoid generation, medical applications, and the generation of in vitro cultivated meat. However, they are limited by high costs, vascular O2 provision, and the resultant inhibition of 3D tissue formation. Effective media usage along with oxygenation and waste management to extend culture health and longevity are key to improving all three. Microalgae, utilizing organic or inorganic CO2, produce O2 from light which complements oxygen-consuming and CO2-respiring mammalian cells and tissue culture. However, common microalgal cultivation conditions differ in temperature and salinity from mammalian cell cultivation environments, making co-cultivation short-lived and challenging. We screened several different microalgae species to identify locally isolated Chlorella BDH-1 as candidate that has high growth rates in mammalian culture conditions while, unlike other Chlorella species, does not compete for glucose as an energy source. In mammalian cell co-culture, BDH1 reduces cellular waste products, stabilizes pH, doubles culture longevity, increases growth performance up to 80%, and reduces expensive and ethically challenging foetal bovine serum requirements. Chlorella BDH-1 was also non-inflammatory and tolerant of clinical antibiotics. Collectively, mammalian cell/BDH1 co-cultivation improves tissue culture health and reduces costs, paving the path for applications in the biotechnology and medical sectors.

cell biology↗

bioRxiv2017

Systems Biology Analysis Using A Genome-Scale Metabolic Model Shows That Phosphine Triggers Global Metabolic Suppression In A Resistant Strain Of C. elegans

BackgroundPest insects are increasingly resistant to phosphine gas, which is used globally to protect grain reserves. The enzyme dihydrolipoamide dehydrogenase (DLD) is a phosphine resistance factor and participates in four key steps of core metabolism, making it a potential central metabolic regulator.\n\nResultsHere we used microarray data and NMR-based metabolomics to characterize the phosphine response of wild-type C. elegans and the phosphine-resistant strain dld-1(wr4) which has a partial loss-of-function mutation in the gene for DLD. In addition, we have constructed CeCon, a C. elegans genome-scale metabolic model to facilitate integration of gene expression and metabolomics data.\n\nConclusionsThe resulting systems biology analysis is consistent with the hypothesis that adaptation to a hypometabolic state is the most prominent mechanism of phosphine resistance in this nematode strain. The involvement of DLD in regulating and creating hypometabolic adaptation has implications for other biological phenomena involving hypometabolism, such as reperfusion injury and metabolic resistance.

systems biology↗