Title: Reductive iron assimilation and intracellular siderophores assist extracellular siderophore-driven iron homeostasis and virulence Authors
Submitted to: Molecular Plant-Microbe Interactions
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 10, 2014
Publication Date: August 1, 2014
Citation: Condon, B.J., Oide, S., Gibson, D.M., Krasnoff, S., Turgeon, B.G. 2014. Reductive iron assimilation and intracellular siderophores assist extracellular siderophore-driven iron homeostasis and virulence. Molecular Plant-Microbe Interactions. 27:793-808. Interpretive Summary: Iron is an important nutrient for all organisms and is one of the essential nutrients sought by pathogens during an invasion of a host. In fungi, small molecules called siderophores allow the pathogen to acquire iron with high affinity, but there is also an additional less efficient mechanism that reduces iron for assimilation. In this study, we used a series of mutants to understand the functional aspects of each gene involved in supplying iron and the various defects of each mutation for the biological functioning of the organism. These defects included fungal virulence, fungal morphology and development, and sensitivity to oxidative stress. The results of this study establish a clear role for siderophores in plant-pathogen interactions by providing the essential nutrient iron to the fungus during infection, however, the reductive iron assimilation pathway does provide a critical backup for viability of the fungus.
Technical Abstract: Iron is an essential nutrient and prudent iron acquisition and management are key traits of a successful pathogen. Fungi use nonribosomally synthesized secreted iron chelators (siderophores) or Reductive Iron Assimilation (RIA) mechanisms to acquire iron in a high affinity manner. Previous studies with the maize pathogen, Cochliobolus heterostrophus, identified two genes, NPS2 and NPS6, encoding different nonribosomal peptide synthetases (NRPS) responsible for biosynthesis of intra- and extra-cellular siderophores, respectively. Deletion of NPS6 results in loss of extracellular siderophore biosynthesis, attenuated virulence, hypersensitivity to oxidative and iron-depletion stress, and reduced asexual sporulation, while nps2 mutants are phenotypically wild type in all of these traits, but defective in sexual spore development when NPS2 is missing from both mating partners. Here it is reported that nps2nps6 mutants have combined and more severe phenotypes than both nps2 and nps6 single mutants. In contrast, mutants lacking the FTR1 or FET3 genes encoding the permease and ferroxidase components, respectively, of the alternate RIA system, are like wild type in all of the above phenotypes. However, without supplemental iron, combinatorial nps6ftr1 and nps2nps6ftr1 mutants, are less virulent, reduced in growth and less able to combat oxidative stress and to sporulate asexually, compared to nps6 mutants alone. These findings demonstrate that while the role of RIA in metabolism and virulence is overshadowed by that of extracellular siderophores as a high affinity iron acquisition mechanism in C. heterostrophus, it functions as a critical backup for the fungus.