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Species of mosquitoes that
transmit malaria (Anopheles gambiae) and the viral fever of the
West Nile virus (Culex pipiens) share the same mutation, which
confers resistance to the most widely used insecticides. This finding
was revealed recently by a team of researchers in Montpellier, France
(Mylène Weill et al., Institut des sciences de l’évolution,
CNRS - Université de Montpellier II). Their discovery is crucial
to combat the growing number of resistant mosquitoes throughout the world.
It is published in the May 8 issue of the journal Nature.
Most insecticides used to combat vectors of disease
in order to slow the transmission to humans of such diseases are organophosphates
and carbamates that inhibit an enzyme, acetylcholinesterase (AChE).
For several years mosquitoes have shown resistance to these pesticides
due to a modification of the AChE.
The acetylcholinesterase gene involved in such resistance was recently
identified and given the name ace-1. Researchers have analyzed this gene
and examined the mutations responsible for resistance among Culex pipiens
found in 10 countries in the Americas, Europe and Africa, and among Anopheles
gambiae found in the Ivory Coast. Their findings indicate that the same
mutation is present in the ace-1 gene of the various species of mosquito.
This point mutation (which corresponds to one base being replaced by another
in the DNA chain) leads to the production of a protein in which one amino
acid is substituted for another (the amino acid glycine is replaced by
a serine: mutation G119S).
In vitro tests carried out on cultured cells have confirmed that this
mutation was indeed responsible for the resistance to the pesticides being
used (insensitivity to carbamate propoxur).
In-depth analysis of the ace-1 gene enabled the researchers to observe
that the G119S mutation has occurred independently at least twice in Culex
pipiens. In addition, since this mutation is found in most mosquito
populations across the globe, it appears likely that the researchers now
hold one of the keys to the origin of mosquitoes' resistance to pesticides
(and even to other types of resistance among various insects, such as
aphids).
This research is fundamental for the development of new strategies to
combat these insects, such as, for example, designing new insecticides
that are able to specifically inhibit mutant acetylcholinesterase.
Mylène Weill and her team have filed a patent concerning the mutant
AchE involved in the mosquitoes' resistance, with the goal of finding
new molecules that are able to inhibit the action of this enzyme. They
plan to use routine screening of this protein in chemical molecule libraries
until they have identified the candidate(s) that can stop its activity.
At stake is a major health and economic issue, one that may be compared
to pharmaceutical research in infectiology, which is constantly striving
to find new classes of antibiotics that are able to bypass the multiple
forms of microbial resistance that have appeared following the intensive
use of longstanding antibiotic families.
Researcher contact:
Mylène Weill
Tel: +33 4 67 14 32 62
E-mail: weill@isem.univ-montp2.fr
Press contact:
Muriel Ilous
Tel: +33 1 44 96 43 09
E-mail: muriel.ilous@cnrs-dir.fr
CNRS Department of Life Sciences contact:
Françoise Tristani
Tel: +33 1 44 96 40 26
E-mail: francoise.tristani@cnrs-dir.fr
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