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Development of a new air-stable structure-simplified nafuredin-gamma analog as a potent and selective nematode complex I inhibitor
Nafuredin-γ, obtained from natural nafuredin, has demonstrated a potent and selective inhibitory activity against nematode complex I. However, nafuredin-γ is unstable in air since its conjugated dienes are oxygen-labile. The instability in air was naturally solved by the synthesis of structure-simplified nafuredin-γ analogs without conjugated dienes. However, these modified analogs showed lower complex I inhibitory activities. Therefore, new air-stable structure-simplified nafuredin-γ analogs were designed and synthesized herein. Among all analogs synthesized, the one bearing a unique 1-azabicyclo[3.1.0]hexane scaffold showed the highest inhibitory activity (IC 50 =170 nM) while presenting high selectivity against nematode complex I.
Journal Article
Real life
Wallace has spent his summer in the lab breeding a strain of microscopic worms for an experiment, a slow and painstaking process. He is four years into a biochemistry degree at a lakeside Midwestern university, a life that's a world away from his childhood growing up in Alabama. His father died a few weeks ago, but Wallace has not been home, and he hasn't told his friends Miller, Yngve, Cole and Emma. For reasons of self-preservation, he has become used to keeping a wary distance even from those closest to him. Over the course of one blustery end-of-summer weekend, a catastrophic mishap and a series of intense confrontations force Wallace to grapple with intimacy, desire, the trauma of the past, and the question of the future. Elegant, brutal and startlingly intimate, Real Life is a campus novel about learning to live from an electric new voice in fiction.
The Fight against Plant-Parasitic Nematodes: Current Status of Bacterial and Fungal Biocontrol Agents
Plant-parasitic nematodes (PPNs) are among the most notorious and underrated threats to food security and plant health worldwide, compromising crop yields and causing billions of dollars of losses annually. Chemical control strategies rely heavily on synthetic chemical nematicides to reduce PPN population densities, but their use is being progressively restricted due to environmental and human health concerns, so alternative control methods are urgently needed. Here, we review the potential of bacterial and fungal agents to suppress the most important PPNs, namely Aphelenchoides besseyi, Bursaphelenchus xylophilus, Ditylenchus dipsaci, Globodera spp., Heterodera spp., Meloidogyne spp., Nacobbus aberrans, Pratylenchus spp., Radopholus similis, Rotylenchulus reniformis, and Xiphinema index.
Journal Article
Increasing importance of anthelmintic resistance in European livestock: creation and meta-analysis of an open database
Helminth infections are ubiquitous in grazing ruminant production systems, and are responsible for significant costs and production losses. Anthelmintic Resistance (AR) in parasites is now widespread throughout Europe, although there are still gaps in our knowledge in some regions and countries. AR is a major threat to the sustainability of modern ruminant livestock production, resulting in reduced productivity, compromised animal health and welfare, and increased greenhouse gas emissions through increased parasitism and farm inputs. A better understanding of the extent of AR in Europe is needed to develop and advocate more sustainable parasite control approaches. A database of European published and unpublished AR research on gastrointestinal nematodes (GIN) and liver fluke (Fasciola hepatica) was collated by members of the European COST Action “COMBAR” (Combatting Anthelmintic Resistance in Ruminants), and combined with data from a previous systematic review of AR in GIN. A total of 197 publications on AR in GIN were available for analysis, representing 535 studies in 22 countries and spanning the period 1980–2020. Reports of AR were present throughout the European continent and some reports indicated high within-country prevalence. Heuristic sample size-weighted estimates of European AR prevalence over the whole study period, stratified by anthelmintic class, varied between 0 and 48%. Estimated regional (country) prevalence was highly heterogeneous, ranging between 0% and 100% depending on livestock sector and anthelmintic class, and generally increased with increasing research effort in a country. In the few countries with adequate longitudinal data, there was a tendency towards increasing AR over time for all anthelmintic classes in GIN: aggregated results in sheep and goats since 2010 reveal an average prevalence of resistance to benzimidazoles (BZ) of 86%, macrocyclic lactones except moxidectin (ML) 52%, levamisole (LEV) 48%, and moxidectin (MOX) 21%. All major GIN genera survived treatment in various studies. In cattle, prevalence of AR varied between anthelmintic classes from 0–100% (BZ and ML), 0–17% (LEV) and 0–73% (MOX), and both Cooperia and Ostertagia survived treatment. Suspected AR in F. hepatica was reported in 21 studies spanning 6 countries. For GIN and particularly F. hepatica, there was a bias towards preferential sampling of individual farms with suspected AR, and research effort was biased towards Western Europe and particularly the United Kingdom. Ongoing capture of future results in the live database, efforts to avoid bias in farm recruitment, more accurate tests for AR, and stronger appreciation of the importance of AR among the agricultural industry and policy makers, will support more sophisticated analyses of factors contributing to AR and effective strategies to slow its spread.
Journal Article
Plant parasitic cyst nematodes redirect host indole metabolism via NADPH oxidase-mediated ROS to promote infection
• Reactive oxygen species (ROS) generated in response to infections often activate immune responses in eukaryotes including plants. In plants, ROS are primarily produced by plasma membrane-bound NADPH oxidases called respiratory burst oxidase homologue (Rboh). Surprisingly, Rbohs can also promote the infection of plants by certain pathogens, including plant parasitic cyst nematodes.
• The Arabidopsis genome contains 10 Rboh genes (RbohA–RbohJ). Previously, we showed that cyst nematode infection causes a localised ROS burst in roots, mediated primarily by RbohD and RbohF. We also found that plants deficient in RbohD and RbohF (rbohD/F) exhibit strongly decreased susceptibility to cyst nematodes, suggesting that Rboh-mediated ROS plays a role in promoting infection. However, little information is known of the mechanism by which Rbohs promote cyst nematode infection.
• Here, using detailed genetic and biochemical analyses, we identified WALLS ARE THIN1 (WAT1), an auxin transporter, as a downstream target of Rboh-mediated ROS during parasitic infections. We found that WAT1 is required to modulate the host’s indole metabolism, including indole-3-acetic acid levels, in infected cells and that this reprogramming is necessary for successful establishment of the parasite.
• In conclusion, this work clarifies a unique mechanism that enables cyst nematodes to use the host’s ROS for their own benefit.
Journal Article
Ecology and Evolution of Soil Nematode Chemotaxis
Plants influence the behavior of and modify community composition of soil-dwelling organisms through the exudation of organic molecules. Given the chemical complexity of the soil matrix, soil-dwelling organisms have evolved the ability to detect and respond to these cues for successful foraging. A key question is how specific these responses are and how they may evolve. Here, we review and discuss the ecology and evolution of chemotaxis of soil nematodes. Soil nematodes are a group of diverse functional and taxonomic types, which may reveal a variety of responses. We predicted that nematodes of different feeding guilds use host-specific cues for chemotaxis. However, the examination of a comprehensive nematode phylogeny revealed that distantly related nematodes, and nematodes from different feeding guilds, can exploit the same signals for positive orientation. Carbon dioxide (CO
2
), which is ubiquitous in soil and indicates biological activity, is widely used as such a cue. The use of the same signals by a variety of species and species groups suggests that parts of the chemo-sensory machinery have remained highly conserved during the radiation of nematodes. However, besides CO
2
, many other chemical compounds, belonging to different chemical classes, have been shown to induce chemotaxis in nematodes. Plants surrounded by a complex nematode community, including beneficial entomopathogenic nematodes, plant-parasitic nematodes, as well as microbial feeders, are thus under diffuse selection for producing specific molecules in the rhizosphere that maximize their fitness. However, it is largely unknown how selection may operate and how belowground signaling may evolve. Given the paucity of data for certain groups of nematodes, future work is needed to better understand the evolutionary mechanisms of communication between plant roots and soil biota.
Journal Article