Know more

Our use of cookies

Cookies are a set of data stored on a user’s device when the user browses a web site. The data is in a file containing an ID number, the name of the server which deposited it and, in some cases, an expiry date. We use cookies to record information about your visit, language of preference, and other parameters on the site in order to optimise your next visit and make the site even more useful to you.

To improve your experience, we use cookies to store certain browsing information and provide secure navigation, and to collect statistics with a view to improve the site’s features. For a complete list of the cookies we use, download “Ghostery”, a free plug-in for browsers which can detect, and, in some cases, block cookies.

Ghostery is available here for free:

You can also visit the CNIL web site for instructions on how to configure your browser to manage cookie storage on your device.

In the case of third-party advertising cookies, you can also visit the following site:, offered by digital advertising professionals within the European Digital Advertising Alliance (EDAA). From the site, you can deny or accept the cookies used by advertising professionals who are members.

It is also possible to block certain third-party cookies directly via publishers:

Cookie type

Means of blocking

Analytical and performance cookies

Google Analytics

Targeted advertising cookies


The following types of cookies may be used on our websites:

Mandatory cookies

Functional cookies

Social media and advertising cookies

These cookies are needed to ensure the proper functioning of the site and cannot be disabled. They help ensure a secure connection and the basic availability of our website.

These cookies allow us to analyse site use in order to measure and optimise performance. They allow us to store your sign-in information and display the different components of our website in a more coherent way.

These cookies are used by advertising agencies such as Google and by social media sites such as LinkedIn and Facebook. Among other things, they allow pages to be shared on social media, the posting of comments, and the publication (on our site or elsewhere) of ads that reflect your centres of interest.

Our EZPublish content management system (CMS) uses CAS and PHP session cookies and the New Relic cookie for monitoring purposes (IP, response times).

These cookies are deleted at the end of the browsing session (when you log off or close your browser window)

Our EZPublish content management system (CMS) uses the XiTi cookie to measure traffic. Our service provider is AT Internet. This company stores data (IPs, date and time of access, length of the visit and pages viewed) for six months.

Our EZPublish content management system (CMS) does not use this type of cookie.

For more information about the cookies we use, contact INRA’s Data Protection Officer by email at or by post at:

24, chemin de Borde Rouge –Auzeville – CS52627
31326 Castanet Tolosan CEDEX - France

Dernière mise à jour : Mai 2018

Menu Institut Sophia Agrobiotech Logo Marque Etat - République Française Logo_INRAE_noir Logo Université Côte d'Azur CNRS

Home page

Institut Sophia Agrobiotech

UMR INRA - Univ. Nice Sophia Antipolis - Cnrs

PLOS Pathogens

18 June 2018

PLOS Pathogens
Deciphering the molecular determinants of cholinergic anthelmintic sensitivity in nematodes: When novel functional validation approaches highlight major differences between the model Caenorhabditis elegans and parasitic species


Cholinergic agonists such as levamisole and pyrantel are widely used as anthelmintics to treat parasitic nematode infestations. These drugs elicit spastic paralysis by activating acetylcholine receptors (AChRs) expressed in nematode body wall muscles. In the model nematode Caenorhabditis elegans, genetic screens led to the identification of five genes encoding levamisole-sensitive-AChR (L-AChR) subunits: unc-38unc-63unc-29lev-1 and lev-8. These subunits form a functional L-AChR when heterologously expressed in Xenopus laevis oocytes. Here we show that the majority of parasitic species that are sensitive to levamisole lack a gene orthologous to Celegans lev-8. This raises important questions concerning the properties of the native receptor that constitutes the target for cholinergic anthelmintics. We demonstrate that the closely related ACR-8 subunit from phylogenetically distant animal and plant parasitic nematode species functionally substitutes for LEV-8 in the Celegans L-AChR when expressed in Xenopus oocytes. The importance of ACR-8 in parasitic nematode sensitivity to cholinergic anthelmintics is reinforced by a ‘model hopping’ approach in which we demonstrate the ability of ACR-8 from the hematophagous parasitic nematode Haemonchus contortus to fully restore levamisole sensitivity, and to confer high sensitivity to pyrantel, when expressed in the body wall muscle of Celegans lev-8 null mutants. The critical role of acr-8 to in vivo drug sensitivity is substantiated by the successful demonstration of RNAi gene silencing for Hco-acr-8 which reduced the sensitivity of Hcontortus larvae to levamisole. Intriguingly, the pyrantel sensitivity remained unchanged thus providing new evidence for distinct modes of action of these important anthelmintics in parasitic species versus Celegans. More broadly, this highlights the limits of Celegans as a predictive model to decipher cholinergic agonist targets from parasitic nematode species and provides key molecular insight to inform the discovery of next generation anthelmintic compounds.


Caenorhabditis elegans, Larvae, Small interfering RNAs, Xenopus oocytes, Nematoda, Cholinergics, Gene silencing, Sequence alignment

Blanchard, A., Guégnard, F., Charvet, C.L., Crisford, A., Courtot, E., Sauvé, C., Harmache, A., Duguet, T., O’Connor, V., Castagnone-Sereno, P., et al. (2018). Deciphering the molecular determinants of cholinergic anthelmintic sensitivity in nematodes: When novel functional validation approaches highlight major differences between the model Caenorhabditis elegans and parasitic species. PLOS Pathogens 14, e1006996. DOI: 10.1371/journal.ppat.1006996

Site : iew online >>