Beyond the eye: Kynurenine pathway impairment causes midgut homeostasis dysfunction and survival and reproductive costs in blood-feeding mosquitoes
| Autor: | Vanessa Bottino-Rojas, Igor Ferreira-Almeida, Rodrigo D. Nunes, Xuechun Feng, Thai Binh Pham, Adam Kelsey, Rebeca Carballar-Lejarazú, Valentino Gantz, Pedro L. Oliveira, Anthony A. James |
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| Rok vydání: | 2021 |
| Předmět: |
Mosquito Vectors
Biochemistry Medicinal and Biomolecular Chemistry Rare Diseases Aedes parasitic diseases Genetics Animals Homeostasis monooxygenase Tryptophan metabolism Molecular Biology Kynurenine Kynurenine hydroxylase/monooxygenase fungi Tryptophan Vector-Borne Diseases Culex Infectious Diseases Emerging Infectious Diseases Good Health and Well Being Insect Science Transgenesis Female Biochemistry and Cell Biology Kynurenine hydroxylase Zoology Entomology |
| Zdroj: | Insect biochemistry and molecular biology. 142 |
| ISSN: | 1879-0240 |
| Popis: | Insect ommochrome biosynthesis pathways metabolize tryptophan to generate eye-color pigments and wild-type alleles of pathway genes are useful phenotypic markers in transgenesis studies. Pleiotropic effects of mutations in some genes exert a load on both survival and reproductive success in blood-feeding species. Here, we investigated the challenges imposed on mosquitoes by the increase of tryptophan metabolites resulting from blood meal digestion and the impact of disruptions of the ommochrome biosynthesis pathway. Female mosquitoes with spontaneous and induced mutations in the orthologs of the genes encoding kynurenine hydroxylase in Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus exhibited impaired survival and reproductive phenotypes that varied in type and severity among the species. A compromised midgut permeability barrier function was also observed in An. stephensi. Surprisingly, mutant mosquitoes displayed an increase in microbiota compared to controls that was not accompanied by a general induction of immune genes. Antibiotic treatment rescued some deleterious traits implicating a role for the kynurenine pathway (KP) in midgut homeostasis. Supplemental xanthurenic acid, a KP end-product, rescued lethality and limited microbiota proliferation in Ae. aegypti. These data implicate the KP in the regulation of the host/microbiota interface. These pleiotropic effects on mosquito physiology are important in the development of genetic strategies targeting vector mosquitoes. |
| Databáze: | OpenAIRE |
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