Making sense of sensory behaviors in vector-borne helminths

Wheeler, Nicolas J; Hallem, Elissa A.; Zamanian, Mostafa

doi:10.1016/j.pt.2022.07.003

Cited by 4 publications

(4 citation statements)

References 114 publications

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“…GPCRs are the largest superfamily of transmembrane receptors, and they have been proven as suitable drug targets in different organisms, including helminths ( 56 – 62 ). Some studies in S. mansoni have reported about GPCR involvement in neuromuscular processes ( 63 ), reproduction ( 25 ), and chemosensation ( 64 ). Former transcriptomic studies in references ( 37 , 43 , 65 ) indicated the existence of 116–117 GPCRs in S. mansoni , including a platyhelminth-specific rhodopsin subfamily, while a recent update pointed to 126 GPCRs ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

Rhodopsin orphan GPCR20 interacts with neuropeptides and directs growth, sexual differentiation, and egg production in female Schistosoma mansoni

Li,

Weth,

Haimann

et al. 2024

Microbiol Spectr

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Schistosomes are parasitic flatworms that cause schistosomiasis, a neglected tropical disease of worldwide importance. Since standard treatment of schistosomiasis relies on a single drug, praziquantel, alternative drugs are needed. G protein-coupled receptors (GPCRs) represent promising targets for new anthelmintics. Although GPCRs represent a prominent receptor class in schistosomes, functional studies are limited just as knowledge about their ligands. Candidate ligands are neuropeptides acting as neurotransmitters, neuromodulators, or hormones in the nervous system. Transcriptomics studies in Schistosoma mansoni indicated that nearly all neuropeptide genes ( Sm_npps ) and a subgroup of GPCRs exhibited a sex- and pairing-dependent expression profile. Among these was the rhodopsin orphan GPCR20 ( Sm GPCR20), which we characterized in our study. Using a yeast two-hybrid-based approach, we identified specific interactions between Sm GPCR20 and two neuropeptides Sm NPP26 and Sm NPP40. As analyzed by qRT-PCR, Smgpcr20 , Smnpp26 , and Smnpp40 showed sex- and/or pairing-influenced expression. Whole-mount in situ hybridization exhibited transcripts of these genes in neuronal cells, subtegumental area, and parenchyma of both sexes. Furthermore, we received indication for co-localization of transcripts of these genes in the anterior “head” region of single-sex females and in particular patterns along the worm body indicating neuronal expression. RNA interference (RNAi) with combinations of double-stranded RNAs against the three genes resulted in reduced egg production. Confocal microscopy revealed morphologic changes in the female gonads. Furthermore, RNAi in first-time paired females caused a reduced length of females after double knockdown of Sm GPCR20 and Sm NPP26 and changes in the ovary. In addition, we found reduced transcript levels of egg formation-associated and gonad-specifically transcribed genes and the stem-cell marker nanos-1 . The obtained results suggest that Sm NPP26 and Sm NPP40 are potential ligands of Sm GPCR20 and that this GPCR in combination with both neuropeptides affects egg production, oogenesis, and growth of S. mansoni females. IMPORTANCE Schistosomes cause schistosomiasis, one of the neglected tropical diseases as defined by the WHO. For decades, the treatment of schistosomiasis relies on a single drug, praziquantel. Due to its wide use, there is justified fear of resistance against this drug, and a vaccine is not available. Besides its biological relevance in signal transduction processes, the class of G protein-coupled receptors (GPCRs) is also well suited for drug design. Against this background, we characterized one GPCR of Schistosoma mansoni , Sm GPCR20, at the molecular and functional level. We identified two potential neuropeptides (NPPs) as ligands, Sm NPP26 and Sm NPP40, and unraveled their roles, in combination with Sm GPCR20, in neuronal processes controlling egg production, oogenesis, and growth of S. mansoni females. Since eggs are closely associated with the pathogenesis of schistosomiasis, our results contribute to the understanding of processes leading to egg production in schistosomes, which is under the control of pairing in this exceptional parasite.

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Section: Discussionmentioning

confidence: 99%

Rhodopsin orphan GPCR20 interacts with neuropeptides and directs growth, sexual differentiation, and egg production in female Schistosoma mansoni

Li,

Weth,

Haimann

et al. 2024

Microbiol Spectr

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“…The concept that helminths use chemical signals to navigate within the host to their preferred site has been known for decades. However, it is becoming increasingly apparent that helminths also use chemicals to recognize, locate, and differentiate suitable hosts and to distinguish infected from uninfected hosts (see Wheeler et al 2022). In digeneans, miracidia change their behaviour in the presence of cues released from competent host snails but not from non-host species.…”

Section: The Parasite Lensmentioning

confidence: 99%

“…Mosquitoes with non-infective first (L 1 ) and second (L 2 ) stage Brugia malayi larvae were less attracted to human chemical cues than mosquitoes with infective third stage (L 3 ) larvae, indicating a co-evolved relationship that promotes filarial transmission (Gleave et al 2016). Release of L 3 larvae from mosquitoes while feeding may involve mechanical, thermal, and chemical cues (Wheeler et al 2022).…”

Section: Helminths Perceive Chemical Signals From the Hostmentioning

confidence: 99%

Helminth-host-environment interactions: Looking down from the tip of the iceberg

Scott

2023

J. Helminthol.

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In 1978, the theory behind helminth parasites having the potential to regulate the abundance of their host populations was formalized based on the understanding that those helminth macroparasites that reduce survival or fecundity of the infected host population would be among the forces limiting unregulated host population growth. Now, 45 years later, a phenomenal breadth of factors that directly or indirectly affect the host–helminth interaction has emerged. Based largely on publications from the past 5 years, this review explores the host–helminth interaction from three lenses: the perspective of the helminth, the host, and the environment. What biotic and abiotic as well as social and intrinsic host factors affect helminths? What are the negative, and positive, implications for host populations and communities? What are the larger-scale implications of the host–helminth dynamic on the environment, and what evidence do we have that human-induced environmental change will modify this dynamic? The overwhelming message is that context is everything. Our understanding of second-, third-, and fourth-level interactions is extremely limited, and we are far from drawing generalizations about the myriad of microbe-helminth-host interactions.Yet the intricate, co-evolved balance and complexity of these interactions may provide a level of resilience in the face of global environmental change. Hopefully, this albeit limited compilation of recent research will spark new interdisciplinary studies, and application of the One Health approach to all helminth systems will generate new and testable conceptual frameworks that encompass our understanding of the host–helminth–environment triad.

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“…Disrupting worm sensation is a potential route for parasite treatment and control, and mutations associated with nematode sensory structures are associated with anthelmintic resistance in C. elegans (Dent et al, 2000;Page, 2018;Wheeler et al, 2022). The mechanism of action of ivermectin against helminths is complex and likely varies based on the species and stage of the parasite it is acting on.…”

Section: Ivermectin Reduces the Gustatory Ability Of Vector-borne Par...mentioning

confidence: 99%

A high-throughput nematode sensory assay reveals an inhibitory effect of ivermectin on parasite gustation

Nunn

Juang

Beebe

et al. 2023

Preprint

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Sensory pathways first elucidated in Caenorhabditis elegans are conserved across free-living and parasitic nematodes, even though each species responds to a diverse array of compounds. Most nematode sensory assays are performed by tallying observations of worm behavior on two-dimensional planes using agarose plates. These assays have been successful in the study of volatile sensation but are poorly suited for investigation of water-soluble gustation or parasitic nematodes without a free-living stage. In contrast, gustatory assays tend to be tedious, often limited to the manipulation of a single individual at a time. We have designed a nematode sensory assay using a microfluidics device that allows for the study of gustation in a 96-well, three-dimensional environment. This device is suited for free-living worms and parasitic worms that spend their lives in an aqueous environment, and we have used it to show that ivermectin inhibits the gustatory ability of vector-borne parasitic nematodes.

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Making sense of sensory behaviors in vector-borne helminths

Cited by 4 publications

References 114 publications

Rhodopsin orphan GPCR20 interacts with neuropeptides and directs growth, sexual differentiation, and egg production in female Schistosoma mansoni

Rhodopsin orphan GPCR20 interacts with neuropeptides and directs growth, sexual differentiation, and egg production in female Schistosoma mansoni

Helminth-host-environment interactions: Looking down from the tip of the iceberg

A high-throughput nematode sensory assay reveals an inhibitory effect of ivermectin on parasite gustation

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