RsmA regulates Aspergillus fumigatus gliotoxin cluster metabolites including cyclo(L-Phe-L-Ser), a potential new diagnostic marker for invasive aspergillosis.
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Output type: Journal article
Author list: Sekonyela, Palmer, Bok, Jain, Berthier, Forseth, Schroeder, Keller
Publisher: Public Library of Science
Publication year: 2013
Journal: PLoS ONE (1932-6203)
Journal acronym: PLOS ONE
Volume number: 8
Issue number: 5
Number of pages: 10
ISSN: 1932-6203
eISSN: 1932-6203
Languages: English-Great Britain (EN-GB)
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Open access status: gold
Full text URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0062591&type=printable
Abstract
Dimeric basic leucine zipper (bZIP) proteins are conserved transcriptional enhancers found in all eukaryotes. A recently reported and novel function for bZIPs is association of these proteins with secondary metabolite production in filamentous fungi. In particular a Yap-like bZIP termed RsmA (restorer of secondary metabolism A) was identified in Aspergillus nidulans that positively regulates the carcinogen sterigmatocystin. To assess for conserved function for RsmA, we examined a role of this protein in secondary metabolism in the pathogen A. fumigatus. RsmA was found to positively regulate gliotoxin where overexpression (OE) of rsmA led to 2-100 fold increases of twelve gli cluster metabolites in culture medium including the newly identified gli metabolite cyclo(L-Phe-L-Ser). Lungs from both wild type and OErsmA infected mice contained gliotoxin (2.3 fold higher in OErsmA treatment) as well as the gliotoxin precursor cyclo(L-Phe-L-Ser) (3.2 fold higher in OErsmA treatment). The data here presents a conserved role for RsmA in secondary metabolite cluster activation and suggests cyclo(L-Phe-L-Ser) may serve as an alternative marker for diagnosis of invasive aspergillosis.
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