PMID- 26929401 OWN - NLM STAT- MEDLINE DCOM- 20170608 LR - 20201209 IS - 1470-8728 (Electronic) IS - 0264-6021 (Linking) VI - 473 IP - 9 DP - 2016 May 1 TI - Identification of ferrichrome- and ferrioxamine B-mediated iron uptake by Aspergillus fumigatus. PG - 1203-13 LID - 10.1042/BCJ20160066 [doi] AB - 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. CI - (c) 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society. FAU - Park, Yong-Sung AU - Park YS AD - School of Life Sciences and Biotechnology, Korea University Anam-dong, Sungbuk-gu, Seoul, Republic of Korea. FAU - Kim, Ju-Yeon AU - Kim JY AD - School of Life Sciences and Biotechnology, Korea University Anam-dong, Sungbuk-gu, Seoul, Republic of Korea. FAU - Yun, Cheol-Won AU - Yun CW AD - School of Life Sciences and Biotechnology, Korea University Anam-dong, Sungbuk-gu, Seoul, Republic of Korea cheolwony@korea.ac.kr. LA - eng PT - Journal Article DEP - 20160229 PL - England TA - Biochem J JT - The Biochemical journal JID - 2984726R RN - 0 (Ferric Compounds) RN - 0 (Fungal Proteins) RN - 0 (Membrane Transport Proteins) RN - 0 (Virulence Factors) RN - 15630-64-5 (Ferrichrome) RN - 4A0UG9NR9K (ferrioxamine B) RN - E1UOL152H7 (Iron) RN - J06Y7MXW4D (Deferoxamine) SB - IM MH - Animals MH - Aspergillus fumigatus/genetics/*metabolism/pathogenicity MH - Cell Membrane/genetics/*metabolism MH - Deferoxamine/*metabolism MH - Ferric Compounds/*metabolism MH - Ferrichrome/*metabolism MH - Fungal Proteins/genetics/metabolism MH - Iron/*metabolism MH - Membrane Transport Proteins/genetics/metabolism MH - Mice MH - Virulence Factors/genetics/*metabolism OTO - NOTNLM OT - Aspergillus fumigatus OT - Saccharomyces cerevisiae OT - iron OT - siderophore OT - sit1 OT - sit2 EDAT- 2016/03/02 06:00 MHDA- 2017/06/09 06:00 CRDT- 2016/03/02 06:00 PHST- 2015/12/04 00:00 [received] PHST- 2016/02/26 00:00 [accepted] PHST- 2016/03/02 06:00 [entrez] PHST- 2016/03/02 06:00 [pubmed] PHST- 2017/06/09 06:00 [medline] AID - BCJ20160066 [pii] AID - 10.1042/BCJ20160066 [doi] PST - ppublish SO - Biochem J. 2016 May 1;473(9):1203-13. doi: 10.1042/BCJ20160066. Epub 2016 Feb 29.