Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0024530 (
malaria
)
44,886
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Chemosensory proteins (CSPs) are a class of small proteins expressed only in arthropods and endowed with heterogeneous functions. Some of them are involved in chemical communications, others in development or other physiological roles. The numbers of CSPs in different species of insects range from 4 in Drosophila to at least 70 in locusts, whereas in other arthropods such as crustaceans and millipedes, only 2-3 very similar sequences have been reported in each species. We have expressed, in a bacterial system, 5 of the 8 CSPs predicted by the genome of the
malaria
mosquito Anopheles gambiae, 4 identified at the protein level (SAP1,
SAP2
, SAP3, and CSP3) and a fifth annotated as part of this work, obtaining the proteins with high yields and in their soluble forms. Purified CSPs have been used to study their ligand-binding properties, both using competitive binding assays and quenching of intrinsic tryptophan fluorescence, in order to get insights into their physiological functions. The agreement between the 2 sets of data supports the assumptions that the ligands, including the fluorescent reporter, bind within the core of the proteins. Their different affinities toward a set of pure chemicals suggest specific roles in chemical communication.
...
PMID:Ligand-binding study of Anopheles gambiae chemosensory proteins. 2359 17
Pyrethroid-impregnated bed nets have driven considerable reductions in
malaria
-associated morbidity and mortality in Africa since the beginning of the century
1
. The intense selection pressure exerted by bed nets has precipitated widespread and escalating resistance to pyrethroids in African Anopheles populations, threatening to reverse the gains that been made by
malaria
control
2
. Here we show that expression of a sensory appendage protein (
SAP2
), which is enriched in the legs, confers pyrethroid resistance to Anopheles gambiae. Expression of
SAP2
is increased in insecticide-resistant populations and is further induced after the mosquito comes into contact with pyrethroids.
SAP2
silencing fully restores mortality of the mosquitoes, whereas
SAP2
overexpression results in increased resistance, probably owing to high-affinity binding of
SAP2
to pyrethroid insecticides. Mining of genome sequence data reveals a selective sweep near the
SAP2
locus in the mosquito populations of three West African countries (Cameroon, Guinea and Burkina Faso) with the observed increase in haplotype-associated single-nucleotide polymorphisms mirroring the increasing resistance of mosquitoes to pyrethroids reported in Burkina Faso. Our study identifies a previously undescribed mechanism of insecticide resistance that is likely to be highly relevant to
malaria
control efforts.
...
PMID:A sensory appendage protein protects malaria vectors from pyrethroids. 3193 51