Proteome interrogation using gold nanoprobes to identify targets of arctigenin in fish parasites

Abstract

Gold nanoparticles (GNPs) are one of the most widely used nanomaterials in various fields. Especially, the unique chemical and physical properties make them as the promising candidates in drug target identification, unfortunately, little is known about their application in parasites. In this paper, GNPs were employed as new solid support to identify drug targets of natural bioactive compound arctigenin (ARG) against fish monogenean parasite Gyrodactylus kobayashi. Before target identification, GNPs with ARG on the surface showed the ability to enter the live parasites even the nucleus or mitochondria, which made the bound compounds capable of contacting directly with target proteins located anywhere of the parasites. At the same time, chemically modified compound remained the anthelminthic efficacy against G. kobayashii. The above results both provide assurance on the reliability of using GNPs for drug target-binding specificity. Subsequently, by interrogating the cellular proteome in parasite lysate, myosin-2 and UNC-89 were identified as the potential direct target proteins of ARG in G. kobayashii. Moreover, results of RNA-seq transcriptomics and iTRAQ proteomics indicated that myosin-2 expressions were down-regulated after ARG bath treatment both in transcript and protein levels, but for UNC-89, only in mRNA level. Myosin-2 is an important structural muscle protein expressed in helminth tegument and its identification as our target will enable further inhibitor optimization towards future drug discovery. Furthermore, our findings demonstrate the power of GNPs to be readily applied to other parasite drugs of unknown targets, facilitating more broadly therapeutic drug design in any pathogen or disease model.

Comparative Proteomics Analysis of Anisakis simplex s.s.—Evaluation of the Response of Invasive Larvae to Ivermectin

“…Myosin is a motor protein that is essential for a variety of processes ranging from intracellular transport to muscle contraction [ 43 ]. Literature data and our results show that antiparasitic drugs, e.g., ivermectin or arctigenin [ 44 ], downregulate the protein level of myosin over time (viz., a significant reduction of protein level from 12 to 24 h of the culture), but compared to the control without IVM, the level of myosin was upregulated ( Figure 3 B). Additionally, Fasciola hepatica ’s susceptibility to the anthelminthic drug triclabendazole, characterized by lethal activity, was indicated by the presence of actin, also one of the motor proteins.…”

Synthesis and anti‐parasites efficacy of coumarin derivatives against Dactylogyrus intermedius

“…Coumarins and arctigenin are a class of phenylpropanoid compounds that have anti‐parasitic targets in the cutaneous muscle structure or mitochondria of parasites. Tu et al used gold nanoparticles as probes to identify myosin‐2 and muscle M‐line assembly protein UNC‐89 as the targets of arctigenin against Gyrodactylus kobayashii (Monogenea) (Tu et al, 2020). Both of these proteins are involved in maintaining the normal structure of myosin.…”

Biological Activity of Gold Compounds against Viruses and Parasitosis: A Systematic Review

“…Plasmonium falciparum and Leishmania infantum Gold(I) complexes combined with triclosan [41,42] Protozoa and Helminth infections Gold(I) complex [43] Leishmania major, Toxoplasma gondii and Trypanosoma brucei parasites Gold(I)-carbene complexes [44] Trichomonas vaginalis Gold Complexes: gold(I) phosphine derivatives [45] Helmintic Gold(I) nanoparticles [46] L. amazenensis and L. braziliensis Gold(I) and gold(III) complexes [47] BioChem 2022, 2, FOR PEER REVIEW 7…”