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The fungal alkaloid Okaramine-B activates an L-glutamate-gated chloride channel from Ixodes scapularis, a tick vector of Lyme disease.

ABSTRACT: A novel L-glutamate-gated anion channel (IscaGluCl1) has been cloned from the black-legged tick, Ixodes scapularis, which transmits multiple pathogens including the agents of Lyme disease and human granulocytic anaplasmosis. When mRNA encoding IscaGluCl1 was expressed in Xenopus laevis oocytes, we detected robust 50-400?nA currents in response to 100??M L-glutamate. Responses to L-glutamate were concentration-dependent (pEC50 3.64?±?0.11). Ibotenate was a partial agonist on IscaGluCl1. We detected no response to 100??M aspartate, quisqualate, kainate, AMPA or NMDA. Ivermectin at 1??M activated IscaGluCl1, whereas picrotoxinin (pIC50 6.20?±?0.04) and the phenylpyrazole fipronil (pIC50 6.90?±?0.04) showed concentration-dependent block of the L-glutamate response. The indole alkaloid okaramine B, isolated from fermentation products of Penicillium simplicissimum (strain AK40) grown on okara pulp, activated IscaGluCl1 in a concentration-dependent manner (pEC50 5.43?±?0.43) and may serve as a candidate lead compound for the development of new acaricides.

SUBMITTER: Furutani S

PROVIDER: S-EPMC6039357 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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The fungal alkaloid Okaramine-B activates an L-glutamate-gated chloride channel from Ixodes scapularis, a tick vector of Lyme disease.

Furutani Shogo S Ihara Makoto M Lees Kristin K Buckingham Steven D SD Partridge Frederick A FA David Jonathan A JA Patel Rohit R Warchal Scott S Mellor Ian R IR Matsuda Kazuhiko K Sattelle David B DB

International journal for parasitology. Drugs and drug resistance 20180604 2

A novel L-glutamate-gated anion channel (IscaGluCl1) has been cloned from the black-legged tick, Ixodes scapularis, which transmits multiple pathogens including the agents of Lyme disease and human granulocytic anaplasmosis. When mRNA encoding IscaGluCl1 was expressed in Xenopus laevis oocytes, we detected robust 50-400 nA currents in response to 100 μM L-glutamate. Responses to L-glutamate were concentration-dependent (pEC<sub>50</sub> 3.64 ± 0.11). Ibotenate was a partial agonist on IscaGluCl1 ...[more]

PMID: 29957333

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Project description:BackgroundThe emergence of vector-borne pathogens in novel geographic areas is regulated by the migration of their arthropod vectors. Blacklegged ticks (Ixodes scapularis) and the pathogens they vector, including the causative agents of Lyme disease, babesiosis and anaplasmosis, continue to grow in their population sizes and to expand in geographic range. Migration of this vector over the previous decades has been implicated as the cause of the re-emergence of the most prevalent infectious diseases in North America.MethodsWe systematically collected ticks from across New York State (hereafter referred to as New York) from 2004 to 2017 as part of routine tick-borne pathogen surveillance in the state. This time frame corresponds with an increase in range and incidence of tick-borne diseases within New York. We randomly sampled ticks from this collection to explore the evolutionary history and population dynamics of I. scapularis. We sequenced the mitochondrial genomes of each tick to characterize their current and historical spatial genetic structure and population growth using phylogeographic methods.ResultsWe sequenced whole mitochondrial genomes from 277 ticks collected across New York between 2004 and 2017. We found evidence of population genetic structure at a broad geographic scale due to differences in the relative abundance, but not the composition, of haplotypes among sampled ticks. Ticks were often most closely related to ticks from the same and nearby collection sites. The data indicate that both short- and long-range migration events shape the population dynamics of blacklegged ticks in New York.ConclusionsWe detailed the population dynamics of the blacklegged tick (Ixodes scapularis) in New York during a time frame in which tick-borne diseases were increasing in range and incidence. Migration of ticks occurred at both coarse and fine scales in the recent past despite evidence of limits to gene flow. Past and current tick population dynamics have implications for further range expansion as habitat suitability for ticks changes due to global climate change. Analyses of mitochondrial genome sequencing data will expound upon previously identified drivers of tick presence and abundance as well as identify additional drivers. These data provide a foundation on which to generate testable hypotheses on the drivers of tick population dynamics occurring at finer scales.

Dataset Information

The fungal alkaloid Okaramine-B activates an L-glutamate-gated chloride channel from Ixodes scapularis, a tick vector of Lyme disease.

Publications

The fungal alkaloid Okaramine-B activates an L-glutamate-gated chloride channel from Ixodes scapularis, a tick vector of Lyme disease.

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