Abstract
Iron is an essential nutrient for all organisms. For pathogenic fungi, iron is essential for the success of infection. Thus, these organisms have developed high affinity iron uptake mechanisms to deal with metal deprivation imposed by the host. Siderophore production is one of the mechanisms that fungal pathogens employ for iron acquisition. Paracoccidioides spp. present orthologous genes encoding the enzymes necessary for the biosynthesis of hydroxamates, and plasma membrane proteins related to the transport of these molecules. All these genes are induced in iron deprivation. In addition, it has been observed that Paracoccidioides spp. are able to use siderophores to scavenge iron. Here we observed that addition of the xenosiderophore ferrioxamine B FOB) to P. brasiliensis culture medium results in repression (at RNA and protein levels) of the SidA, the first enzyme of the siderophore biosynthesis pathway. Furthermore, SidA activity was reduced in the presence of FOB, suggesting that P. brasiliensis blocks siderophores biosynthesis and can explore siderophores in the environment to scavenge iron. In order to support the importance of siderophores on Paracoccidioides sp. life and infection cycle, silenced mutants for the sidA gene were obtained by antisense RNA technology. The obtained AsSidA strains displayed decreased siderophore biosynthesis in iron deprivation conditions and reduced virulence to an invertebrate model.
Highlights
Iron is an essential nutrient for growth and development of living organisms
Molecular modeling of SidA demonstrates its interaction with substrates for the first step in siderophore biosynthesis P. brasiliensis has orthologs for the all the components for siderophore biosynthesis, the functionality of this pathway still remains elusive
The molecular modeling and three-dimensional structure comparison was based on A. fumigatus SidA displaying 47% identity with P. brasiliensis putative SidA ortholog
Summary
Iron is an essential nutrient for growth and development of living organisms. Due to iron redox properties, this metal occurs in two oxidation states, ferrous ion (Fe+ 2) and ferric ion (Fe+ 3), which are influenced by pH and oxygen (Sanchez et al 2017). Nutritional immunity (i.e., host deprivation of metals, such Fe, Cu, Mn and Zn) is an important mechanism employed by the host to control the development of pathogenic organisms, to overcome the low availability of iron imposed by the host, microorganisms developed high affinity mechanisms for iron uptake (Raymond et al 2003). In fungal pathogens these mechanisms include: the reduction of Fe+ 3 to Fe+ 2, the acquisition of the iron bound to the heme group, and the solubilization of Fe+ 3 promoted by siderophores
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
