Aspergillus fumigatus is an opportunistic fungal pathogen for immunocompromised patients, and genes involved in siderophore metabolism have been identified as virulence factors. Recently, we identified the membrane transporters sit1 and sit2, which are putative virulence factors of A. fumigatus; sit1 and sit2 are homologous to yeast Sit1, and sit1 and sit2 gene expression was up-regulated after iron depletion. When expressed heterologously in Saccharomyces cerevisiae, sit1 and sit2 were localized to the plasma membrane; sit1 efficiently complemented ferrichrome (FC) and ferrioxamine B (FOB) uptake in yeast cells, whereas sit2 complemented only FC uptake. Deletion of sit1 resulted in a decrease in FOB and FC uptake, and deletion of sit2 resulted in a decrease in FC uptake in A. fumigatus. It is of interest that a sit1 and sit2 double-deletion mutant resulted in a synergistic decrease in FC uptake activity. Both sit1 and sit2 were localized to the plasma membrane in A. fumigatus. The expression levels of the sit1 and sit2 genes were dependent on hapX under low-but not high-iron conditions. Furthermore, mirB, and sidA gene expression was up-regulated and sreA expression down-regulated when sit1 and sit2 were deleted. Although sit1 and sit2 failed to affect mouse survival rate, these genes affected conidial killing activity. Taken together, our results suggest that sit1 and sit2 are siderophore transporters and putative virulence factors localized to the plasma membrane.
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May 2016
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The biological dimer of MurIMtb shown as a protein cartoon. Interface residues that form hydrogen bonding interactions or salt links are highlighted in purple and yellow. For further details see pp. 1267-1280. Image kindly provided by Kurt Krause. - PDF Icon PDF LinkFront Matter
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Research Article|
April 26 2016
Identification of ferrichrome- and ferrioxamine B-mediated iron uptake by Aspergillus fumigatus
Yong-Sung Park;
Yong-Sung Park
1
*School of Life Sciences and Biotechnology, Korea University Anam-dong, Sungbuk-gu, Seoul, Republic of Korea
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Ju-Yeon Kim;
Ju-Yeon Kim
1
*School of Life Sciences and Biotechnology, Korea University Anam-dong, Sungbuk-gu, Seoul, Republic of Korea
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Cheol-Won Yun
Cheol-Won Yun
2
*School of Life Sciences and Biotechnology, Korea University Anam-dong, Sungbuk-gu, Seoul, Republic of Korea
2To whom correspondence should be addressed (email cheolwony@korea.ac.kr).
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Publisher: Portland Press Ltd
Received:
December 04 2015
Revision Received:
February 24 2016
Accepted:
February 26 2016
Accepted Manuscript online:
February 29 2016
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2016
Biochem J (2016) 473 (9): 1203–1213.
Article history
Received:
December 04 2015
Revision Received:
February 24 2016
Accepted:
February 26 2016
Accepted Manuscript online:
February 29 2016
Citation
Yong-Sung Park, Ju-Yeon Kim, Cheol-Won Yun; Identification of ferrichrome- and ferrioxamine B-mediated iron uptake by Aspergillus fumigatus. Biochem J 1 May 2016; 473 (9): 1203–1213. doi: https://doi.org/10.1042/BCJ20160066
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