Feedback

Thermal proteome profiling reveals Haemonchus orphan protein HCO_011565 as a target of the nematocidal small molecule UMW-868

Affiliation
Department of Veterinary Biosciences ,Faculty of Veterinary and Agricultural Sciences ,Melbourne Veterinary School ,The University of Melbourne ,Parkville ,VIC ,Australia
Taki, Aya C.;
Affiliation
Department of Veterinary Biosciences ,Faculty of Veterinary and Agricultural Sciences ,Melbourne Veterinary School ,The University of Melbourne ,Parkville ,VIC ,Australia
Wang, Tao;
Affiliation
Walter and Eliza Hall Institute of Medical Research ,Parkville ,VIC ,Australia
Nguyen, Nghi N.;
Affiliation
Melbourne Mass Spectrometry and Proteomics Facility ,The Bio21 Molecular Science and Biotechnology Institute ,The University of Melbourne ,Parkville ,VIC ,Australia
Ang, Ching-Seng;
Affiliation
Melbourne Mass Spectrometry and Proteomics Facility ,The Bio21 Molecular Science and Biotechnology Institute ,The University of Melbourne ,Parkville ,VIC ,Australia
Leeming, Michael G.;
Affiliation
Melbourne Mass Spectrometry and Proteomics Facility ,The Bio21 Molecular Science and Biotechnology Institute ,The University of Melbourne ,Parkville ,VIC ,Australia
Nie, Shuai;
Affiliation
Department of Veterinary Biosciences ,Faculty of Veterinary and Agricultural Sciences ,Melbourne Veterinary School ,The University of Melbourne ,Parkville ,VIC ,Australia
Byrne, Joseph J.;
Affiliation
Department of Veterinary Biosciences ,Faculty of Veterinary and Agricultural Sciences ,Melbourne Veterinary School ,The University of Melbourne ,Parkville ,VIC ,Australia
Young, Neil D.;
Affiliation
Department of Veterinary Biosciences ,Faculty of Veterinary and Agricultural Sciences ,Melbourne Veterinary School ,The University of Melbourne ,Parkville ,VIC ,Australia
Zheng, Yuanting;
Affiliation
Department of Veterinary Biosciences ,Faculty of Veterinary and Agricultural Sciences ,Melbourne Veterinary School ,The University of Melbourne ,Parkville ,VIC ,Australia
Ma, Guangxu;
Affiliation
Department of Veterinary Biosciences ,Faculty of Veterinary and Agricultural Sciences ,Melbourne Veterinary School ,The University of Melbourne ,Parkville ,VIC ,Australia
Korhonen, Pasi K.;
Affiliation
Department of Veterinary Biosciences ,Faculty of Veterinary and Agricultural Sciences ,Melbourne Veterinary School ,The University of Melbourne ,Parkville ,VIC ,Australia
Koehler, Anson V.;
Affiliation
Melbourne Mass Spectrometry and Proteomics Facility ,The Bio21 Molecular Science and Biotechnology Institute ,The University of Melbourne ,Parkville ,VIC ,Australia
Williamson, Nicholas A.;
Affiliation
Department of Veterinary Biosciences ,Faculty of Veterinary and Agricultural Sciences ,Melbourne Veterinary School ,The University of Melbourne ,Parkville ,VIC ,Australia
Hofmann, Andreas;
Affiliation
Department of Veterinary Biosciences ,Faculty of Veterinary and Agricultural Sciences ,Melbourne Veterinary School ,The University of Melbourne ,Parkville ,VIC ,Australia
Chang, Bill C. H.;
Affiliation
Medical Parasitology and Infection Biology ,Swiss Tropical and Public Health Institute ,Allschwil ,Switzerland
Häberli, Cécile;
Affiliation
Medical Parasitology and Infection Biology ,Swiss Tropical and Public Health Institute ,Allschwil ,Switzerland
Keiser, Jennifer;
Affiliation
Department of Veterinary Biosciences ,Faculty of Veterinary and Agricultural Sciences ,Melbourne Veterinary School ,The University of Melbourne ,Parkville ,VIC ,Australia
Jabbar, Abdul;
Affiliation
Department of Veterinary Biosciences ,Faculty of Veterinary and Agricultural Sciences ,Melbourne Veterinary School ,The University of Melbourne ,Parkville ,VIC ,Australia
Sleebs, Brad E.;
Affiliation
Department of Veterinary Biosciences ,Faculty of Veterinary and Agricultural Sciences ,Melbourne Veterinary School ,The University of Melbourne ,Parkville ,VIC ,Australia
Gasser, Robin B.

Parasitic roundworms (nematodes) cause destructive diseases, and immense suffering in humans and other animals around the world. The control of these parasites relies heavily on anthelmintic therapy, but treatment failures and resistance to these drugs are widespread. As efforts to develop vaccines against parasitic nematodes have been largely unsuccessful, there is an increased focus on discovering new anthelmintic entities to combat drug resistant worms. Here, we employed thermal proteome profiling (TPP) to explore hit pharmacology and to support optimisation of a hit compound (UMW-868), identified in a high-throughput whole-worm, phenotypic screen. Using advanced structural prediction and docking tools, we inferred an entirely novel, parasite-specific target (HCO_011565) of this anthelmintic small molecule in the highly pathogenic, blood-feeding barber’s pole worm, and in other socioeconomically important parasitic nematodes. The “hit-to-target” workflow constructed here provides a unique prospect of accelerating the simultaneous discovery of novel anthelmintics and associated parasite-specific targets.

Cite

Citation style:
Could not load citation form.

Access Statistic

Total:
Downloads:
Abtractviews:
Last 12 Month:
Downloads:
Abtractviews:

Rights

License Holder: Copyright © 2022 Taki, Wang, Nguyen, Ang, Leeming, Nie, Byrne, Young, Zheng, Ma, Korhonen, Koehler, Williamson, Hofmann, Chang, Häberli, Keiser, Jabbar, Sleebs and Gasser.

Use and reproduction: