NDLI: Discovery of a highly synergistic anthelmintic combination that shows mutual hypersusceptibility

Content Provider	PubMed Central
Author	Hu, Yan Platzer, Edward G. Audrey, Bellier Aroian, Raffi V.
Abstract	The soil-transmitted helminths or nematodes (hookworms, whipworms, and Ascaris) are roundworms that infect more than 1 billion of the poorest peoples and are leading causes of morbidity worldwide. Few anthelmintics are available for treatment, and only one is commonly used in mass drug administrations. New anthelmintics are urgently needed, and crystal (Cry) proteins made by Bacillus thuringiensis are promising new candidates. Combination drug therapies are considered the ideal treatment for infectious diseases. Surprisingly, little work has been done to define the characteristics of anthelmintic combinations. Here, by means of quantitative assays with wild-type and mutants of the roundworm Caenorhabditis elegans, we establish a paradigm for studying anthelmintic combinations using Cry proteins and nicotinic acetylcholine receptor (nAChR) agonists, e.g., tribendimidine and levamisole. We find that nAChR agonists and Cry proteins, like Cry5B and Cry21A, mutually display what is known in the HIV field as hypersusceptibility—when the nematodes become resistant to either class, they become hypersensitive to the other class. Furthermore, we find that when Cry5B and nAChR agonists are combined, their activities are strongly synergistic, producing combination index values as good or better than seen with antitumor, anti-HIV, and insecticide combinations. Our study provides a powerful means by which anthelmintic combination therapies can be examined and demonstrate that the combination of nAChR agonists and Cry proteins has excellent properties and is predicted to give improved cure rates while being recalcitrant to the development of parasite resistance.
Related Links	http://dx.doi.org/10.1073/pnas.0912327107
Ending Page	5960
Page Count	6
Starting Page	5955
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	13
Volume Number	107
Language	English
Publisher	National Academy of Sciences
Publisher Date	2010-03-30
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

An anthelmintic compound, nafuredin, shows selective inhibition of complex I in helminth mitochondria

Highly Effective Fibrinolysis by a Sequential Synergistic Combination of Mini-Dose tPA plus Low-Dose Mutant proUK

Discovery of a p53 variant that controls metastasis

Photosynthetic metabolism of C3 plants shows highly cooperative regulation under changing environments: A systems biological analysis

Avermectin B1a, a paralyzing anthelmintic that affects interneurons and inhibitory motoneurons in Ascaris.

Quantifying causal emergence shows that macro can beat micro

Hypersusceptibility of cystic fibrosis mice to chronic Pseudomonas aeruginosa oropharyngeal colonization and lung infection

Highly conserved proteins that modify plant ethylene responses

Dictyostelium discoideum has a highly Q/N-rich proteome and shows an unusual resilience to protein aggregation

Discovery of a highly synergistic anthelmintic combination that shows mutual hypersusceptibility

Similar Documents

An anthelmintic compound, nafuredin, shows selective inhibition of complex I in helminth mitochondria

Highly Effective Fibrinolysis by a Sequential Synergistic Combination of Mini-Dose tPA plus Low-Dose Mutant proUK

Discovery of a p53 variant that controls metastasis

Photosynthetic metabolism of C3 plants shows highly cooperative regulation under changing environments: A systems biological analysis

Avermectin B1a, a paralyzing anthelmintic that affects interneurons and inhibitory motoneurons in Ascaris.

Quantifying causal emergence shows that macro can beat micro

Hypersusceptibility of cystic fibrosis mice to chronic Pseudomonas aeruginosa oropharyngeal colonization and lung infection

Highly conserved proteins that modify plant ethylene responses

Dictyostelium discoideum has a highly Q/N-rich proteome and shows an unusual resilience to protein aggregation

Discovery of a highly synergistic anthelmintic combination that shows mutual hypersusceptibility