Uptake of the Siderophore Triacetylfusarinine C, but Not Fusarinine C, Is Crucial for Virulence of Aspergillus fumigatus

Abstract

Aspergillus fumigatus is responsible for thousands of cases of invasive fungal disease annually. For iron uptake, A. fumigatus secretes so-called siderophores, which are taken up after the binding of environmental iron.

The Siderophore Ferricrocin Mediates Iron Acquisition in Aspergillus fumigatus

“…The t ranscript l evels (TLs) of most characterized genes involved in SIA increased significantly during the 8-h germination process but showed different patterns, which were largely similar in both A. fumigatus strains analyzed, AfIR974 and AfIR964. Interestingly, the genes exclusively involved in TAFC metabolism ( 9 , 20 ), TAFC transporter-encoding mirB (AFUA_3G03640) and the transacetylase-encoding sidG (AFUA_3G03650), showed very low TLs up to 6 h after initiation of germination before they significantly increased ( Fig. 2A ).…”

“…2A ). sidF (AFUA_3G03400), sidH (AFUA_3G03410), sidI (AFUA_1G17190), and mirD (AFUA_3G03440), which are involved in biosynthesis and uptake of fusarinine-type siderophores ( 6 , 9 , 14 , 20 ), had higher TLs in conidia (0-h time point), followed by a faster increase ( Fig. 2B ).…”

“…In contrast, in the late germination phase (early hyphal growth, 6 to 8 h after initiation of germination), the transcript levels of siderophore biosynthetic genes were responsive to the environmental iron availability, suggesting iron regulation. Remarkably, genes involved in TAFC biosynthesis ( sidG ) and uptake ( mirB ) had a very low conidial TLs, and their expression increased only in the late germination phase ( 9 , 20 ). Taken together, these data indicated a role of FC biosynthesis and uptake in germination, as illustrated in Fig.…”

“…The task of extracellular siderophores is chelation of ambient iron for cellular uptake. Iron chelated by fusarinine C and TAFC is imported by the siderophore transporters MirD and MirB, respectively, and MirB has been shown to be crucial for virulence of A. fumigatus ( 19 , 20 ). Notably, A. fumigatus employs two additional siderophore transporters, termed Sit1 and Sit2.…”

The Oxidative Stress Response Highly Depends on Glucose and Iron Availability in Aspergillus fumigatus

“…It may provide a safe iron supply in an imbalanced redox milieu. Concurring with these data, deletion of mirB (TAF-C transporter gene), sidA (ornithine monooxygenase gene involved in extra- and intracellular siderophore biosynthesis) were found to be crucial for virulence [ 56 , 57 ], while the absence of active sidI , sidH , sidF , sidD (elements of the extracellular siderophore cluster) or sidC (element of the intracellular siderophore gene cluster) genes but not ftrA (iron permease, element of RIA) also attenuated virulence [ 40 , 57 , 58 ]. In addition to siderophore metabolism, appropriate activity of Fe-S cluster assembly appears to also be important since Fe-S cluster assembly genes and Fe-S cluster binding protein genes were enriched in the upregulated gene set in three out of the four studied culturing conditions ( Table 2 and Table S3 ).…”