Distinct roles for intra- and extracellular siderophores during Aspergillus fumigatus infection.
Siderophore biosynthesis by the highly lethal mould Aspergillus fumigatus is essential for virulence, but non-existent in humans, presenting a rare opportunity to strategize therapeutically against this pathogen. We have previously demonstrated that A. fumigatus excretes fusarinine C and triacetylfu...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2007-09-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.0030128&type=printable |
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| author | Markus Schrettl Elaine Bignell Claudia Kragl Yasmin Sabiha Omar Loss Martin Eisendle Anja Wallner Herbert N Arst Ken Haynes Hubertus Haas |
| author_facet | Markus Schrettl Elaine Bignell Claudia Kragl Yasmin Sabiha Omar Loss Martin Eisendle Anja Wallner Herbert N Arst Ken Haynes Hubertus Haas |
| author_sort | Markus Schrettl |
| collection | DOAJ |
| description | Siderophore biosynthesis by the highly lethal mould Aspergillus fumigatus is essential for virulence, but non-existent in humans, presenting a rare opportunity to strategize therapeutically against this pathogen. We have previously demonstrated that A. fumigatus excretes fusarinine C and triacetylfusarinine C to capture extracellular iron, and uses ferricrocin for hyphal iron storage. Here, we delineate pathways of intra- and extracellular siderophore biosynthesis and show that A. fumigatus synthesizes a developmentally regulated fourth siderophore, termed hydroxyferricrocin, employed for conidial iron storage. By inactivation of the nonribosomal peptide synthetase SidC, we demonstrate that the intracellular siderophores are required for germ tube formation, asexual sporulation, resistance to oxidative stress, catalase A activity, and virulence. Restoration of the conidial hydroxyferricrocin content partially rescues the virulence of the apathogenic siderophore null mutant Delta sidA, demonstrating an important role for the conidial siderophore during initiation of infection. Abrogation of extracellular siderophore biosynthesis following inactivation of the acyl transferase SidF or the nonribosomal peptide synthetase SidD leads to complete dependence upon reductive iron assimilation for growth under iron-limiting conditions, partial sensitivity to oxidative stress, and significantly reduced virulence, despite normal germ tube formation. Our findings reveal distinct cellular and disease-related roles for intra- and extracellular siderophores during mammalian Aspergillus infection. |
| format | Article |
| id | doaj-art-bba175b549eb4c239cf95aa34c11cc84 |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2007-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-bba175b549eb4c239cf95aa34c11cc842025-02-12T05:30:43ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742007-09-01391195120710.1371/journal.ppat.0030128Distinct roles for intra- and extracellular siderophores during Aspergillus fumigatus infection.Markus SchrettlElaine BignellClaudia KraglYasmin SabihaOmar LossMartin EisendleAnja WallnerHerbert N ArstKen HaynesHubertus HaasSiderophore biosynthesis by the highly lethal mould Aspergillus fumigatus is essential for virulence, but non-existent in humans, presenting a rare opportunity to strategize therapeutically against this pathogen. We have previously demonstrated that A. fumigatus excretes fusarinine C and triacetylfusarinine C to capture extracellular iron, and uses ferricrocin for hyphal iron storage. Here, we delineate pathways of intra- and extracellular siderophore biosynthesis and show that A. fumigatus synthesizes a developmentally regulated fourth siderophore, termed hydroxyferricrocin, employed for conidial iron storage. By inactivation of the nonribosomal peptide synthetase SidC, we demonstrate that the intracellular siderophores are required for germ tube formation, asexual sporulation, resistance to oxidative stress, catalase A activity, and virulence. Restoration of the conidial hydroxyferricrocin content partially rescues the virulence of the apathogenic siderophore null mutant Delta sidA, demonstrating an important role for the conidial siderophore during initiation of infection. Abrogation of extracellular siderophore biosynthesis following inactivation of the acyl transferase SidF or the nonribosomal peptide synthetase SidD leads to complete dependence upon reductive iron assimilation for growth under iron-limiting conditions, partial sensitivity to oxidative stress, and significantly reduced virulence, despite normal germ tube formation. Our findings reveal distinct cellular and disease-related roles for intra- and extracellular siderophores during mammalian Aspergillus infection.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.0030128&type=printable |
| spellingShingle | Markus Schrettl Elaine Bignell Claudia Kragl Yasmin Sabiha Omar Loss Martin Eisendle Anja Wallner Herbert N Arst Ken Haynes Hubertus Haas Distinct roles for intra- and extracellular siderophores during Aspergillus fumigatus infection. PLoS Pathogens |
| title | Distinct roles for intra- and extracellular siderophores during Aspergillus fumigatus infection. |
| title_full | Distinct roles for intra- and extracellular siderophores during Aspergillus fumigatus infection. |
| title_fullStr | Distinct roles for intra- and extracellular siderophores during Aspergillus fumigatus infection. |
| title_full_unstemmed | Distinct roles for intra- and extracellular siderophores during Aspergillus fumigatus infection. |
| title_short | Distinct roles for intra- and extracellular siderophores during Aspergillus fumigatus infection. |
| title_sort | distinct roles for intra and extracellular siderophores during aspergillus fumigatus infection |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.0030128&type=printable |
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