@article{fdi:010064642,
  title = {{T}he repellent {DEET} potentiates carbamate effects via insect muscarinic receptor interactions : an alternative strategy to control insect vector-borne diseases},
  author = {{A}bd-{E}lla, {A}. and {S}tankiewicz, {M}. and {M}ikulska, {K}. and {N}owak, {W}. and {P}ennetier, {C}{\'e}dric and {G}oulu, {M}. and {F}ruchart-{G}aillard, {C}. and {L}icznar, {P}. and {A}paire-{M}archais, {V}. and {L}ist, {O}. and {C}orbel, {V}incent and {S}ervent, {D}. and {L}apied, {B}.},
  editor = {},
  language = {{ENG}},
  abstract = {{I}nsect vector-borne diseases remain one of the principal causes of human mortality. {I}n addition to conventional measures of insect control, repellents continue to be the mainstay for personal protection. {B}ecause of the increasing pyrethroid-resistant mosquito populations, alternative strategies to reconstitute pyrethroid repellency and knock-down effects have been proposed by mixing the repellent {DEET} ({N},{N}-{D}iethyl-3-methylbenzamide) with non-pyrethroid insecticide to better control resistant insect vector-borne diseases. {B}y using electrophysiological, biochemichal, in vivo toxicological techniques together with calcium imaging, binding studies and in silico docking, we have shown that {DEET}, at low concentrations, interacts with high affinity with insect {M}1/{M}3 m{AC}h{R} allosteric site potentiating agonist effects on m{AC}h{R}s coupled to phospholipase {C} second messenger pathway. {T}his increases the anticholinesterase activity of the carbamate propoxur through calcium-dependent regulation of acetylcholinesterase. {A}t high concentrations, {DEET} interacts with low affinity on distinct {M}1/{M}3 m{AC}h{R} site, counteracting the potentiation. {S}imilar dose-dependent dual effects of {DEET} have also been observed at synaptic m{AC}h{R} level. {A}dditionally, binding and in silico docking studies performed on human {M}1 and {M}3 m{AC}h{R} subtypes indicate that {DEET} only displays a low affinity antagonist profile on these {M}1/{M}3 m{AC}h{R}s. {T}hese results reveal a selective high affinity positive allosteric site for {DEET} in insect m{AC}h{R}s. {F}inally, bioassays conducted on {A}edes aegypti confirm the synergistic interaction between {DEET} and propoxur observed in vitro, resulting in a higher mortality of mosquitoes. {O}ur findings reveal an unusual allosterically potentiating action of the repellent {DEET}, which involves a selective site in insect. {T}hese results open exciting research areas in public health particularly in the control of the pyrethroid-resistant insect-vector borne diseases. {M}ixing low doses of {DEET} and a non-pyrethroid insecticide will lead to improvement in the efficiency treatments thus reducing both the concentration of active ingredients and side effects for non-target organisms. {T}he discovery of this insect specific site may pave the way for the development of new strategies essential in the management of chemical use against resistant mosquitoes.},
  keywords = {},
  booktitle = {},
  journal = {{P}los {O}ne},
  volume = {10},
  numero = {5},
  pages = {e0126406 [20 p.]},
  ISSN = {1932-6203},
  year = {2015},
  DOI = {10.1371/journal.pone.0126406},
  URL = {https://www.documentation.ird.fr/hor/fdi:010064642},
}