Resistance to oxidative stress via regulating siderophore-mediated iron acquisition by the citrus fungal pathogen Alternaria alternata

Abstract

The ability of the necrotrophic fungus Alternaria alternata to detoxify reactive oxygen species (ROS) is crucial for pathogenesis to citrus. We report regulation of siderophore-mediated iron acquisition and ROS resistance by the NADPH oxidase (NOX), the redox activating yesassociated protein 1 (YAP1) regulator, and the high-osmolarity glycerol 1 (HOG1) mitogenactivated protein kinase (MAPK). The A. alternata nonribosomal peptide synthetase (NPS6) is essential for the biosynthesis of siderophores, contributing to iron uptake under low-iron conditions. Fungal strains impaired for NOX, YAP1, HOG1 or NPS6 all display increased sensitivity to ROS. Exogenous addition of iron at least partially rescues ROS sensitivity seen for NPS6, YAP1, HOG1, and NOX mutants. Importantly, expression of the NPS6 gene and biosynthesis of siderophores are regulated by NOX, YAP1 and HOG1, supporting a functional link among these regulatory pathways. Although iron fully rescues H 2 O 2 sensitivity seen in mutants impaired for the response regulator SKN7, neither expression of NPS6 nor biosynthesis of siderophores is controlled by SKN7. Our results indicate that the acquisition of environmental iron has profound effects on ROS detoxification.

Transcriptome analysis of fungicide-responsive gene expression profiles in two Penicillium italicum strains with different response to the sterol demethylation inhibitor (DMI) fungicide prochloraz

“…The mitogen-activated protein (MAP) kinase signaling pathways, ubiquitously found in eukaryotes (from yeasts to various pathogenic fungi), comprise a set of cascaded protein kinases, MAP kinase kinase kinase (MAPKKK), MAP kinase kinase (MAPKK) and MAP kinase (MAPK), acting in series to modulate target protein activities [63,64]. Three major MAPK signaling pathways, Fus3/Kss1, Hog1, and Slt2, have been revealed in model yeasts [65][66][67] and filamentous fungi, including the citrus pathogens Alternaria alternata [68][69][70][71] and P. digitatum [72,73], regulating pheromone/invasion processes, high osmolarity glycerol anabolism, and stress-induced cell wall remodeling, respectively. Hog1-MAPK (PdOs2)-mediated CWI signaling are involved in P. digitatum resistance to the fungicides iprodione and fludioxonil [72].…”

Endogenous cross-talk of fungal metabolites

“…In Alternaria alternata , deletion of NPS6, a NRPS essential for extracellular siderophore biosynthesis, results in increases sensitivity to H 2 O 2 . In addition, expression of NPS6 in A. alternata is regulated by NOX, YAP1, and HOG1, genes involved in oxidative stress defense ( Chen et al, 2014b ). Deletion of NPS6 in Cochliobolus miyabeanus, Fusarium graminearum , and Alternaria brassicicola also resulted in increased sensitivity to oxidative stress ( Oide et al, 2006 ).…”

A Major Facilitator Superfamily Transporter-Mediated Resistance to Oxidative Stress and Fungicides Requires Yap1, Skn7, and MAP Kinases in the Citrus Fungal Pathogen Alternaria alternata

“…alternata mutant strains lacking the Yap1 transcription activator, the Hog1 mitogen-activated protein (MAP) kinase, the Ssk1 regulator, the Skn7 response regulator, the NADPH oxidase (Nox), or the Gpx3 glutathione peroxidase all displayed hypersensitivity to oxidants and reduced lesion formation on citrus [11,12,14–18]. Exogenous addition of iron partially rescued H 2 O 2 sensitivity seen for Yap1 , Hog1 , Skn7 , and Nox mutants [19], indicating the important role of iron uptake in ROS resistance. This could be attributable to the fact that iron is an important cofactor for antioxidant activities and that iron itself could promote ROS detoxification through a non-enzymatic mechanism.…”