Structure–Activity Relationships Delineate How the Maize PathogenCochliobolus heterostrophusUses Aromatic Compounds as Signals and Metabolites

Abstract

The necrotrophic maize pathogen Cochliobolus heterostrophus senses plant-derived phenolic compounds, which promote nuclear retention of the redox-sensitive transcription factor ChAP1 and alter gene expression. The intradiol dioxygenase gene CCHD1 is strongly upregulated by coumaric and caffeic acids. Plant phenolics are potential nutrients but some of them are damaging compounds that need to be detoxified. Using coumaric acid as an inducer (16 to 160 μM), we demonstrated the rapid and simultaneous upregulation of most of the β-ketoadipate pathway genes in C. heterostrophus. A cchd1 deletion mutant provided genetic evidence that protocatechuic acid is an intermediate in catabolism of a wide range of aromatic acids. Aromatics catabolism was slowed for compounds showing toxicity, and this was strongly correlated with nuclear retention of GFP-ChAP1. The activity of a structure series of compounds showed complementary requirements for upregulation of CCHD1 and for ChAP1 nuclear retention. Thus, there is an inverse correlation between the ability to metabolize a compound and the stress response (ChAP1 nuclear retention) that it causes. The ability to metabolize phenolics and to respond to them as signals should be an advantage to plant pathogens and may explain the presence of at least two response pathways detecting these compounds.

Role of the transcription factor ChAP1 in cytoplasmic redox homeostasis: imaging with a genetically encoded sensor in the maize pathogen Cochliobolus heterostrophus

“…It is, however, in agreement with the lack of induction of antioxidant genes by phenolic compounds. Plant extract does induce ROS‐detoxifying genes (Lev et al ., ; Shalaby et al ., ; Shanmugam et al ., ). Nevertheless, in the presence of plant extract, the intracellular redox state was more reduced than that observed when conidia germinated in water, and similar to the redox state in the presence of phenolics (Fig.…”

“…Thus, the function of this conserved transcriptional regulator appears to have diverged in the co‐evolution of plant pathogens with their hosts, or may depend on additional experimental factors. In C. heterostrophus , phenolic compounds that are found in the plant host promote the nuclear retention of a functional GFP:ChAP1 fusion protein, but do not induce the accumulation of ChAP1‐dependent transcripts (Shalaby et al ., ; Shanmugam et al ., ). In yeast, some phenolics have been found to indirectly activate YAP1 by causing the accumulation of H 2 O 2 (Maeta et al ., ).…”

Genetic interaction of the stress response factors ChAP1 and Skn7 in the maize pathogenCochliobolus heterostrophus

“…The fungus thus must contend with ROS produced by both members of the host-pathogen pair. Skn7 senses not only oxidant stress, but also osmotic and cell wall stresses (Izumitsu et al, 2007;Oide et al, 2010;Fassler & West, 2011), and ChAP1 also appears to have redox-independent sensory functions (Shanmugam et al, 2010;Shalaby et al, 2012). In Candida glabrata, certain combinations of oxidative, nitrosative and osmotic stress were more potent than each alone (Kaloriti et al, 2012).…”

Plant phenolic acids induce programmed cell death of a fungal pathogen: MAPK signaling and survival of Cochliobolus heterostrophus

“…Some genes in this pathway are induced by phenolic substrates, as well as by analogs that are not necessarily metabolized as shown in classic experiments on the genetic model species Neurospora crassa (Gross and Tatum, ) . Substrate induction was found for two plant pathogens (Michielse et al ., ; Shalaby et al ., ). In the Fusarium oxysporum /tomato pathosystem the ability to metabolize phenolics is essential for virulence: F. oxysporum mutants deleted for CMLE, an enzyme in the β‐ketoadipate pathway, are still able to colonize the root surface but lack virulence (Michielse et al ., ).…”

“…cinnamic and benzoic acid). The accumulation of the unmetabolized compound may lead to toxicity (Shalaby et al ., ). These toxic compounds are perceived as a stress, as indicated by nuclear retention of ChAP1, a redox‐sensitive fungal transcription factor with a major contribution to the oxidative stress response (Lev et al ., ; Shanmugam et al ., ; Shalaby et al ., ).…”