Mosquito metallomics reveal copper and iron as critical factors for Plasmodium infection
Por:
Maya-Maldonado, Krystal, Cardoso-Jaime, Victor, Gonzalez-Olvera, Gabriela, Osorio, Beatriz, Recio-Totoro, Benito, Manrique-Saide, Pablo, Rodríguez-Sánchez I.P., Lanz-Mendoza, Humberto, Missirlis, Fanis, Hernández-Hernández F.C.
Publicada:
1 jun 2021
Resumen:
Iron and copper chelation restricts Plasmodium growth in vitro and in
mammalian hosts. The parasite alters metal homeostasis in red blood
cells to its favor, for example metabolizing hemoglobin to hemozoin.
Metal interactions with the mosquito have not, however, been studied.
Here, we describe the metallomes of Anopheles albimanus and Aedes
aegypti throughout their life cycle and following a blood meal.
Consistent with previous reports, we found evidence of maternal iron
deposition in embryos of Ae. aegypti, but less so in An. albimanus.
Sodium, potassium, iron, and copper are present at higher concentrations
during larval developmental stages. Two An. albimanus phenotypes that
differ in their susceptibility to Plasmodium berghei infection were
studied. The susceptible white stripe (ws) phenotype was named after a
dorsal white stripe apparent during larval stages 3, 4, and pupae.
During larval stage 3, ws larvae accumulate more iron and copper than
the resistant brown stripe (bs) phenotype counterparts. A similar
increase in copper and iron accumulation was also observed in the
susceptible ws, but not in the resistant bs phenotype following P.
berghei infection. Feeding ws mosquitoes with extracellular iron and
copper chelators before and after receiving Plasmodium-infected blood
protected from infection and simultaneously affected follicular
development in the case of iron chelation. Unexpectedly, the application
of the iron chelator to the bs strain reverted resistance to infection.
Besides a drop in iron, iron-chelated bs mosquitoes experienced a
concomitant loss of copper. Thus, the effect of metal chelation on P.
berghei infectivity was strain-specific.
Author summary To establish a life cycle between insect and mammalian
hosts, the malaria parasite has evolved mechanisms to manage metal ions
from the distinct microenvironments it encounters. Previous work has
addressed how interference using metal chelation affects parasite
development in human, primate, and rodent hosts. Similar studies in
mosquito species that harbor Plasmodium have not been performed. Here,
we address such micronutrient relationships in three steps. First, we
characterized how the metallome fluctuates during development in two
species of mosquito. Second, we asked whether susceptibility to
Plasmodium infection correlated with a differential response in mosquito
metal homeostasis. Third, we tested the effects of iron and copper
chelation treatment of adult mosquitoes concerning propensity of
infection and mosquito reproduction. Metal ions offer a promising target
in the ongoing efforts to control the mosquito-borne disease.
Filiaciones:
Departamento de Infectómica y Patogénesis Molecular, Cinvestav, Ciudad de México, Mexico
Centro de Investigaciones sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico
Unidad Colaborativa para Bioensayos Entomológicos, Campus de Ciencias Biológicas y Agropecuarias, Universidad Autónoma de Yucatán, Mérida, Yucatán, México
Departamento de Fisiología, Biofísica y Neurociencias, Cinvestav, Ciudad de México, Mexico
Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico
Laboratorio de Fisiología Molecular y Estructural, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico
Green Published, gold, All Open Access, Gold, Green
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