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The control of parasitic nematode infections relies mostly on anthelmintics. The potential pharmacotherapeutic application of phytochemicals, in order to overcome parasite resistance and enhance the effect of existing drugs, is becoming increasingly important. The antinematodal effects of carveol was tested on the free-living nematode Caenorhabditis elegans and the neuromuscular preparation of the parasitic nematode Ascaris suum. Carveol caused spastic paralysis in C. elegans. InA. suum carveol potentiated contractions induced by acetylcholine (ACh) and this effect was confirmed with two-electrode voltage-clamp electrophysiology on the A. suum nicotinic ACh receptor expressed in Xenopus oocytes. However, potentiating effect of carveol on ACh-induced contractions was partially sensitive to atropine, indicates a dominant nicotine effect but also the involvement of some muscarinic structures. The effects of carveol on the neuromuscular system of mammals are also specific. In micromolar concentrations, carveol acts as a noncompetitive ACh antagonist on ileum contractions. Unlike atropine, it does not change the EC50 of ACh, but reduces the amplitude of contractions. Carveol caused an increase in Electrical Field Stimulation-evoked contractions of the isolated rat diaphragm, but at higher concentrations it caused an inhibition. Also, carveol neutralized the mecamylamine-induced tetanic fade, indicating a possibly different pre- and post-synaptic action at the neuromuscular junction. [ABSTRACT FROM AUTHOR]

Natural isolates coming from chemically untreated environmental samples can be a source of new nematocidal bacterial strains. Little is known about the abundance of such isolates; the diversity of nematocidal proteins that they produce, or how their nematocidal activity changes in a growth phase-dependent manner. In this study, a collection of 17 Bacillus thuringiensis (Bt) natural isolates was screened for nematocidal activity and the presence of nematocidal genes (cry1, cry5, cry6, cry12, cry13, cry14, and cry21). Most strains were positive for cry1 and at least one other cry gene. Further, nematocidal activity against Caenorhabditis elegans was detected in 82.35% of strains. This percentage is significantly higher than percentages found in previously reported studies on similar strain collections. We next sought to investigate the correlation between bacterial growth phase and nematocidal activity. All strains clustered into two growth phase-dependent nematocidal activity profiles. 28.57% of nematocidal strains were active from the exponential and throughout the stationary phase. 42.85% of them were active only in the exponential phase. Strains active only in the stationary phase were not observed. A combination of strains active in different growth phases was then used to investigate the possibility of killing entire nematode populations. Complete clearance of nematodes was accomplished after two days of incubation when a mixed culture of two such strains (SS-9.4 and SS-16.2) was used. Therefore, combining Bt strains, which are nematocidal in different growth phases, could ameliorate their application in the biological control of nematodes. [ABSTRACT FROM AUTHOR]

Resistance of parasitic nematodes to anthelmintic drugs is a growing problem in human and veterinary medicine. The molecular mechanisms by which nematodes become resistant are different, but certainly one of the possible processes involves changing the drug binding site on the specific receptor. The significance of changes in individual subtypes of nicotinic acetylcholine receptors (nAChRs) for the development of resistance has not been clarified in detail. This study investigates the interaction of antinematodal drugs, agonist of different types of nAChRs and carvacrol with gamma aminobutyric acid (GABA) on the contractions of parasitic nematode A. suum . In our study, GABA (3 μM) produced significant increase of contractile EC 50 value for pyrantel, and nonsignificant for bephenium and morantel, from 8.44 to 28.11 nM, 0.62 to 0.96 µM, and 3.72 to 5.69 nM, respectively. On the other hand, the maximal contractile effect ( R max ) did not change in the presence of GABA. However, when A. summ muscle flaps were incubated with GABA 3 μM and carvacrol 100 μM, the EC 50 value of pyrantel, bephenium, and morantel was increased significantly to 44.62 nM, 1.40 μM, and nonsignificantly to 7.94 nM, respectively. Furthermore, R max decreased by 70, 60, and 65%. Presented results indicate that the combined use of GABA receptor agonists and nicotinic receptor antagonists can effectively inhibit the neuromuscular system of nematodes, even when one of the nicotinic receptor subtypes is dysfunctional, due to the potential development of resistance., (© 2021 Authors.)