Fungi, fungicide discovery and global food security

Abstract

Securing sufficient food for a growing world population is of paramount importance for social stability and the well-being of mankind. Recently, it has become evident that fungal pathogens pose the greatest biotic challenge to our calorie crops. Moreover, the loss of commodity crops to fungal disease destabilises the economies of developing nations, thereby increasing the dimension of the threat. Our best weapon to control these pathogens is fungicides, but increasing resistance puts us in an arms race against them. New anti-fungal compounds need to be discovered, such as mono-alky lipophilic cations (MALCs) described herein. Collaborations between academia and industry are imperative to establish new and efficient ways to develop these new fungicides and to bring them to the market-place.

Keywords: Crop disease; Food security; Fungi; Fungicides.

Fig. 1

Effect of MALCs on the fungal respiration chain. MALCs consist of a lipophilic n-alkyl chain and a cationic head group. They have an overall lipophilicity, given as the LogP value, that allows passage through cellular membranes (e.g. LogP_Dodine = 2.26, LogP_ATP = −3.39, LogP_{Membrane phospholipid} = +10.19; see Steinberg et al., 2020). Due to their cationic head group, MALCs accumulate in mitochondria, the only negatively-charged organelle in the cell (A). Here, they insert into the inner mitochondrial membrane, which holds the enzymes for cellular respiration and ATP-synthesis. MALCs inhibit NADH oxidation, which involves unique and fungal specific respiratory enzymes (A, NDH-2 = alternative NADH dehydrogenases, Joseph-Horne et al., 2001). The inhibition of mitochondrial respiration reduces cellular ATP levels and, ultimately, kills the pathogen (B). A newly-synthesised MALC (C_18-SMe₂⁺) induces the formation of reactive oxygen species (ROS) at respiratory complex I. This, in turn, activates apoptosis and drives the pathogen to commit “cell suicide” (apoptotic cell death). These multiple modes of action (Video 1) underpin effective protection by C_18-SMe₂⁺ against Septoria tritici blotch in wheat and rice blast disease. The Figure was modified from Steinberg et al. (2020).