The Siderophore Transporters Sit1 and Sit2 Are Essential for Utilization of Ferrichrome-, Ferrioxamine- and Coprogen-Type Siderophores in Aspergillus fumigatus

Abstract

Siderophore-mediated acquisition of iron has been shown to be indispensable for the virulence of several fungal pathogens, the siderophore transporter Sit1 was found to mediate uptake of the novel antifungal drug VL-2397, and siderophores were shown to be useful as biomarkers as well as for imaging of fungal infections. However, siderophore uptake in filamentous fungi is poorly characterized. The opportunistic human pathogen Aspergillus fumigatus possesses five putative siderophore transporters. Here, we demonstrate that the siderophore transporters Sit1 and Sit2 have overlapping, as well as unique, substrate specificities. With respect to ferrichrome-type siderophores, the utilization of ferrirhodin and ferrirubin depended exclusively on Sit2, use of ferrichrome A depended mainly on Sit1, and utilization of ferrichrome, ferricrocin, and ferrichrysin was mediated by both transporters. Moreover, both Sit1 and Sit2 mediated use of the coprogen-type siderophores coprogen and coprogen B, while only Sit1 transported the bacterial ferrioxamine-type xenosiderophores ferrioxamines B, G, and E. Neither Sit1 nor Sit2 were important for the utilization of the endogenous siderophores fusarinine C and triacetylfusarinine C. Furthermore, A. fumigatus was found to lack utilization of the xenosiderophores schizokinen, basidiochrome, rhizoferrin, ornibactin, rhodotorulic acid, and enterobactin. Taken together, this study characterized siderophore use by A. fumigatus and substrate characteristics of Sit1 and Sit2.

Secondary Metabolites Produced during Aspergillus fumigatus and Pseudomonas aeruginosa Biofilm Formation

“…Siderophores are ferric iron chelators, structurally separated into different classes named hydroxamates, catecholates, carboxylates, phenolates, and mixed class. Hydroxamates are subdivided into rhodotorulic acid-, ferrioxamine-, fusarinine-, coprogen-, and ferrichrome-type siderophores and are the ones that are produced by A. fumigatus ( 54 ). In our assay, fusarinine B, coprogen B, and ferrichrome were detected in monoculture and cocultures.…”

Synergistic Antifungal Effect of a Combination of Iron Deficiency and Calcium Supplementation

“…However, further studies are required to investigate the clinical safety of using DFO, since the concentration of DFO used in this study was too high. On the other hand, DFO also supports iron supply of pathogens in mucormycosis in vivo ( 72 , 73 ). Collectively, the findings in this study suggest that a microenvironment with excess calcium and limited iron is an efficient defense strategy to curb the growth of invading pathogens.…”

Secondary metabolites produced during Aspergillus fumigatus and Pseudomonas aeruginosa biofilm formation

“…Siderophores are ferric-iron chelators, structurally separated in different classes named hydroxamates, catecholates, carboxylates, phenolates, and mixed-classes. Hydroxamates are sub-divided into rhodotorulic acid, ferrioxamine-, fusarinine-, coprogen-, and ferrichrome-type siderophores and are the ones that are produced by A. fumigatus (52). In our assay, fusarinine B, coprogen B, and ferrichrome were detected in monoculture and co-cultures.…”