Biology subjects

Brito-Fravallo, E.

Publications and source records attributed to Brito-Fravallo, E..

3 recordsLinked to original sources

bioRxiv2026

Anopheles resistance to deltamethrin can be caused by the increased abundance of an enteric Aeromonas taxon

The enteric bacteriome of Anopheles mosquito vector has been linked with its vectorial competence, however, its influence on insecticide resistance is poorly understood. We found that the depletion of the bacterial microbiome in susceptible Anopheles strains, resulting from antibiotic treatment, led to greater than 50% insecticide deltamethrin tolerance compared to untreated mosquitoes. Simultaneous inhibition of cytochrome P450 activity reverted the antibiotic-induced tolerance phenotype, indicating that the antibiotic-induced deltamethrin tolerance is P450-dependent. We found that the antibiotic treatment, while suppressing most enteric bacterial taxa, allowed proliferation of a particular antibiotic-tolerant Aeromonas taxon, most closely related to Aeromonas hydrophila. Increasing the abundance of this taxon in mosquitoes not treated with antibiotics phenocopied the tolerance phenotype, converting deltamethrin-susceptible Anopheles to deltamethrin-tolerant mosquitoes. Collectively, these results highlight a mechanistic interplay in Anopheles mosquitoes between antibiotic-induced enteric dysbiosis and cytochrome P450-mediated detoxification that promotes insecticide tolerance. This effect could influence mosquito vectorial capacity, especially in Africa, where auto-medication with antibiotics is highly prevalent.

microbiology↗

bioRxiv2022

Rasputin/G3BP mediates o-nyong-nyong virus subversion of antiviral immunity in Anopheles coluzzii

The G3BP proteins in vertebrates and Aedes mosquito ortholog, Rasputin, are essential for alphavirus infection, but the underlying mechanism of Rasputin/G3BP proviral activity is poorly understood. It has been suggested that G3BP could influence host immune signaling, but this has not been functionally demonstrated. Here, we find that depletion of Rasputin activity in Anopheles mosquitoes, the primary vectors of the alphavirus onyong-nyong (ONNV), provokes dysregulation of the antiviral Imd, JAK/STAT and RNAi pathways, indicating that Rasputin is required for expression of normal basal immunity in uninfected mosquitoes. Depletion of Rasputin during ONNV bloodmeal infection causes increased transcript abundance of genes in the Imd pathway including positive regulator Rel2, and decreases ONNV infection in mosquitoes. Loss of Rasputin is complemented by co-depletion of Imd pathway positive regulator, Rel2, which restores normal ONNV infection levels. Thus, the presence of Rasputin is required for ONNV inhibition of Imd activity, and viral inhibition of Imd explains much of the Rasputin proviral activity. The viral non-structural protein 3 (nsP3) binds to Rasputin and alters the profile of cellular proteins binding to Rasputin. In the presence of nsP3, 48 Rasputin-binding proteins are unchanged but seven binding proteins are excluded and eight new proteins bind Rasputin. The Rasputin binding partners altered by nsP3 are candidate factors for ONNV immune manipulation and subversion through Rasputin. Overall, these results are consistent with and strongly suggest a mechanism in which ONNV, probably nsP3, co-opts the normal Rasputin function assuring basal cellular immune activity in order to inhibit antiviral immunity and promote infection. These observations may be generalizable for Rasputin function during alphavirus infection of other mosquitoes, as well as for G3BP function in the mammalian host, and could offer a target for vector-based control of arbovirus transmission.

microbiology↗

bioRxiv2019

The APL1 immune factor is encoded by a single ancestral gene in most Anopheles species and expanded to three paralogs with distinct function in the Anopheles gambiae complex

BackgroundThe recent reference genome assembly and annotation of the Asian malaria vector Anopheles stephensi revealed only one gene encoding the leucine-rich repeat immune factor APL1, while in Anopheles gambiae and sibling Anopheles coluzzii, APL1 factors are encoded by a family of three paralogs. The phylogeny and biological function of the unique APL1 gene in A. stephensi have not yet been specifically examined.\n\nMethodsThe APL1 locus was manually sequenced to confirm the computationally predicted single APL1 gene in A. stephensi, and APL1 evolution within Anopheles was explored by phylogenomic analysis. The single or paralogous APL1 genes were silenced in A. stephensi and A. coluzzii, respectively, followed by mosquito survival analysis, experimental infection with Plasmodium, and expression analysis.\n\nResultsAPL1 is present as a single ancestral gene in most Anopheles including A. stephensi, but has expanded to three paralogs in an African lineage that includes only the Gambiae species complex and Anopheles christyi. Silencing of the unique APL1 copy in A. stephensi results in significant mosquito mortality. Elevated mortality of APL1-depleted A. stephensi is rescued by antibiotic treatment, suggesting that bacteria are the cause of mortality, and that the unique APL1 gene is essential for host survival. Successful Plasmodium development in A. stephensi depends upon APL1 activity for protection from high host mortality, probably caused by exposure to enteric bacteria when parasites cross the midgut epithelial barrier. In contrast, silencing of all three APL1 paralogs in A. coluzzii does not result in elevated mortality, either with or without Plasmodium infection. Expression of the single APL1 gene is regulated by both the Imd and Toll immune pathways, while control by the two pathways is subdivided to different paralogs in the expanded APL1 locus.\n\nConclusionsAPL1 underwent neofunctionalization with both loss and gain of functions concomitant with expansion from a single ancestral gene to three paralogs in one lineage of African Anopheles. The evolution of an expanded APL1 gene family could be a factor contributing to the exceptional levels of malaria transmission mediated by human-feeding members of the Gambiae complex in Africa.

genetics↗