Alkaline pH, Low Iron Availability, Poor Nitrogen Sources and CWI MAPK Signaling Are Associated with Increased Fusaric Acid Production in Fusarium oxysporum

Fusaric acid (FA) is one of the first secondary metabolites isolated from phytopathogenic fungi belonging to the genus Fusarium. This molecule exerts a toxic effect on plants, rhizobacteria, fungi and animals, and it plays a crucial role in both plant and animal pathogenesis. In plants, metal chelation by FA is considered one of the possible mechanisms of action. Here, we evaluated the effect of different nitrogen sources, iron content, extracellular pH and cellular signalling pathways on the production of FA siderophores by the pathogen Fusarium oxysporum (Fol). Our results show that the nitrogen source affects iron chelating activity and FA production. Moreover, alkaline pH and iron limitation boost FA production, while acidic pH and iron sufficiency repress it independent of the nitrogen source. FA production is also positively regulated by the cell wall integrity (CWI) mitogen-activated protein kinase (MAPK) pathway and inhibited by the iron homeostasis transcriptional regulator HapX. Collectively, this study demonstrates that factors promoting virulence (i.e., alkaline pH, low iron availability, poor nitrogen sources and CWI MAPK signalling) are also associated with increased FA production in Fol. The obtained new insights on FA biosynthesis regulation can be used to prevent both Fol infection potential and toxin contamination.

Automated summary

Fusaric acid (FA), a secondary metabolite found in phytopathogenic fungi, has toxic effects on plants, rhizobacteria, fungi, and animals, and is involved in plant and animal pathogenesis. This study investigated the factors affecting FA production in Fusarium oxysporum (Fol), including nitrogen sources, iron content, extracellular pH, and cellular signaling pathways. The results showed that the nitrogen source, extracellular pH, and iron availability influenced FA production, with alkaline pH and iron limitation promoting FA production, while acidic pH and iron sufficiency repressed it. Additionally, the cell wall integrity (CWI) MAPK pathway positively regulated FA production, while the iron homeostasis transcriptional regulator HapX inhibited it. These findings provide new insights into FA biosynthesis regulation and can be utilized to prevent Fol infection and toxin contamination.