Carabrone slows growth of a wheat pathogen by disrupting energy production

Greg Howard
6th October, 2025

Carabrone slows growth of a wheat pathogen by disrupting energy production

Growth of a fungal colony (white) is dramatically halted with increasing concentrations of carabrone from left (Control) to right (400 µM).

Image adapted from: Ren et al. / CC BY (Source)

Key Findings

  • In wheat, carabrone, a plant compound, disrupts energy production within fungal cells, impacting disease development
  • Carabrone reduces the ratio of vital energy molecules NAD⁺ to NADH in the fungus, hindering its metabolism
  • The study identifies mitochondrial respiratory chain complex I as carabrone’s direct target, inhibiting its function and ultimately killing the fungus
Crop diseases caused by fungal pathogens represent a significant and growing threat to global food security[2]. These pathogens cause substantial yield losses in major crops like wheat, rice, maize, potato and soybean, impacting both economic stability and food availability, particularly in regions already facing food deficits[2]. The intensification of agricultural practices, such as monoculture farming, and the globalization of markets contribute to the emergence and spread of new, and increasingly resistant, fungal strains[3]. Furthermore, the overuse of conventional fungicides – chemicals used to control these pathogens – has accelerated the development of fungicide resistance, diminishing their effectiveness[4]. Researchers at Northwest A&F University and the USDA-ARS Plains Area have recently investigated a potential new strategy for combating these fungal infections, focusing on natural compounds produced by plants themselves[1]. Plants aren’t passive victims of fungal attack; they produce a diverse array of chemicals to defend against pathogens. This study centered on a compound called carabrone, a sesquiterpene lactone, and its effects on Gaeumannomyces tritici, a fungus responsible for sharp eyespot disease in wheat. The research team employed a ‘multi-omics’ approach, meaning they analyzed multiple layers of biological information simultaneously. They used transcriptomic profiling – essentially measuring which genes are active in the fungus at different times after exposure to carabrone – to understand how the fungus responds to the compound. This revealed that carabrone strongly suppresses the oxidative phosphorylation (OXPHOS) pathway, a critical process for energy production within the fungal cell, and disrupts nicotinate/nicotinamide metabolism. A key consequence of this disruption was a reduction in the ratio of NAD⁺ to NADH, two molecules vital for cellular energy transfer. To confirm the importance of this NAD⁺/NADH balance, the researchers added extra NAD⁺ to the fungal culture. This supplementation reduced the fungus’s sensitivity to carabrone, directly demonstrating a link between NAD⁺ levels and the compound’s antifungal activity. Further investigation using activity-based protein profiling (ABPP) and gene silencing screens pinpointed the specific target of carabrone: the electron transport chain (ETC), a component of the OXPHOS pathway. The ETC isn’t a single entity, but a series of protein complexes. The study showed carabrone inhibits complex I of the ETC, rather than ATP synthase (another part of the energy production machinery). This inhibition disrupts NADH oxidation, leading to oxidative stress and ultimately, a collapse of the fungus’s energy metabolism. To further validate this, researchers used pyruvate supplementation, which can bypass some of the ETC’s functions, and expressed a yeast protein (ScNDI1) – a non-proton-pumping NADH dehydrogenase – which also mitigated the effects of carabrone. Enzymatic assays then confirmed direct interaction between carabrone and complex I. This work represents a significant step forward in understanding how carabrone kills G. tritici. It’s the first time complex I has been definitively established as the direct antifungal target of this compound. Importantly, the researchers also identified ScNDI1 as a valuable tool for screening other potential fungicides that target complex I. The findings offer a lead scaffold for developing novel complex I inhibitors, and a systematic framework for validating the effectiveness of new antifungal agents, providing a potential route to combat emerging fungal resistance. This is particularly relevant given the increasing issues with fungicide resistance observed in many plant pathogens[4], and the need for alternative control strategies to maintain crop yields and food security[2].

BiochemPlant ScienceMycology

References

Main Study

1) Carabrone inhibits Gaeumannomyces tritici growth by targeting mitochondrial complex I and destabilizing NAD⁺/NADH homeostasis

Published 3rd October, 2025

https://doi.org/10.1371/journal.ppat.1013567

Related Studies

2) The global burden of pathogens and pests on major food crops.

https://doi.org/10.1038/s41559-018-0793-y

3) Threats to global food security from emerging fungal and oomycete crop pathogens.

https://doi.org/10.1038/s43016-020-0075-0

4) Fungicide Resistance: Progress in Understanding Mechanism, Monitoring, and Management.

https://doi.org/10.1094/PHYTO-10-22-0370-KD


Related Articles

An unhandled error has occurred. Reload 🗙