Ketamine can be produced by Pochonia chlamydosporia: an old molecule and a new anthelmintic?

Abstract

Background Infection by nematodes is a problem for human health, livestock, and agriculture, as it causes deficits in host health, increases production costs, and incurs a reduced food supply. The control of these parasites is usually done using anthelmintics, which, in most cases, have not been fully effective. Therefore, the search for new molecules with anthelmintic potential is necessary. Methods In the present study, we isolated and characterized molecules from the nematophagous fungus Pochonia chlamydosporia and tested these compounds on three nematodes: Caenorhabditis elegans; Ancylostoma ceylanicum; and Ascaris suum. Results The ethyl acetate extract showed nematicidal activity on the nematode model C. elegans. We identified the major substance present in two sub-fractions of this extract as ketamine. Then, we tested this compound on C. elegans and the parasites A. ceylanicum and A. suum using hamsters and mice as hosts, respectively. We did not find a difference between the animal groups when considering the number of worms recovered from the intestines of animals treated with ketamine (6 mg) and albendazole (P > 0.05). The parasite burden of larvae recovered from the lungs of mice treated with ketamine was similar to those treated with ivermectin. Conclusions The results presented here demonstrate the nematicidal activity of ketamine in vitro and in vivo, thus confirming the nematicidal potential of the molecule present in the fungus P. chlamydosporia may consist of a new method of controlling parasites.

Natural nematicidal metabolites and advances in their biocontrol capacity on plant parasitic nematodes

“…110 Ketamine 263 was the major nematicidal constituent isolated from the nematophagous fungus Pochonia chlamydosporia , and it exhibited activity against C. elegans . 111 Pigment prodigiosin 264 was extracted from bacterium Serratia marcescens and exhibited activity against the juvenile stages of the plant migratory endoparasitic nematode Radopholus similis and root-knot nematode M. javanica , with LC 50 values of 83 and 79 μg mL −1 , respectively. It also inhibited the nematode egg-hatching ability.…”

Spending Time in Nature: The Overlooked Health Behavior

“…Ketamine is an NMDA receptor antagonist with an anesthetic effect. 24 Although it can be found in nature in certain fungi, 25 the amount produced is so small that it must be synthesized for therapeutic effect. In the 1960s, Belgian scientists manufactured ketamine as an anesthesia medicine for animals.…”

Recent Advances in the Control of Helminths of Domestic Animals by Helminthophagous Fungi

“…There are reports that P. chlamydosporia, in addition to ovicidal action, parasitises female phytonematodes of the genus Meloidogyne, which are colonized and completely digested [28,29]. Several secondary metabolites produced by this fungus have been described as promising to be applied as anthelmintics [30,31]. Intermediate hosts of trematodes, such as the mollusk Pseudosuccinea columella, also have their offspring affected by this fungus [32].…”

“…In the fungus P. chlamidosporia, the secondary metabolite ketamine showed excellent efficacy against A. ceylanicum and A. suum and with similar efficacy to the anthelmintic albendazole [31]. Therefore, future research in the search for new formulations, association of fungi from different groups, extraction of new molecules and nanoparticles are desired.…”