Synthesis of the Hydroxamate Siderophore N-alpha-Methylcoprogen B in Scedosporium apiospermum Is Mediated by sidD Ortholog and Is Required for Virulence

0535071 - MBÚ 2021 RIV CH eng J - Journal Article
Le Govic, Y. - Havlíček, Vladimír - Capilla, J. - Luptáková, Dominika - Dumas, D. - Papon, N. - Le Gal, S. - Bouchara, J.P. - Vandeputte, P.
Synthesis of the Hydroxamate Siderophore N-alpha-Methylcoprogen B in Scedosporium apiospermum Is Mediated by sidD Ortholog and Is Required for Virulence.
Frontiers in Cellular and Infection Microbiology. Roč. 10, OCT28 (2020), č. článku 587909. ISSN 2235-2988. E-ISSN 2235-2988
R&D Projects: GA ČR(CZ) GA19-10907S
Institutional support: RVO:61388971
Keywords : aspergillus-fumigatus * filamentous fungi * iron-metabolism * transformation * biosynthesis * disruption * ku70 * Scedosporium * iron uptake * extracellular siderophore * n945 * methyl coprogen B * xenosiderophores
OECD category: Microbiology
Impact factor: 5.293, year: 2020
Method of publishing: Open access
https://www.frontiersin.org/articles/10.3389/fcimb.2020.587909/full

Scedosporium species rank second among the filamentous fungi capable to colonize chronically the respiratory tract of patients with cystic fibrosis (CF). Nevertheless, there is little information on the mechanisms underpinning their virulence. Iron acquisition is critical for the growth and pathogenesis of many bacterial and fungal genera that chronically inhabit the CF lungs. In a previous study, we showed the presence in the genome of Scedosporium apiospermum of several genes relevant for iron uptake, notably SAPIO_CDS2806, an ortholog of sidD, which drives the synthesis of the extracellular hydroxamate-type siderophore fusarinine C (FsC) and its derivative triacetylfusarinine C (TAFC) in Aspergillus fumigatus. Here, we demonstrate that Scedosporium apiospermum sidD gene is required for production of an excreted siderophore, namely, N-alpha-methylcoprogen B, which also belongs to the hydroxamate family. Blockage of the synthesis of N-alpha-methylcoprogen B by disruption of the sidD gene resulted in the lack of fungal growth under iron limiting conditions. Still, growth of Delta sidD mutants could be restored by supplementation of the culture medium with a culture filtrate from the parent strain, but not from the mutants. Furthermore, the use of xenosiderophores as the sole source of iron revealed that S. apiospermum can acquire the iron using the hydroxamate siderophores ferrichrome or ferrioxamine, i.e., independently of N-alpha-methylcoprogen B production. Conversely, N-alpha-methylcoprogen B is mandatory for iron acquisition from pyoverdine, a mixed catecholate-hydroxamate siderophore. Finally, the deletion of sidD resulted in the loss of virulence in a murine model of scedosporiosis. Our findings demonstrate that S. apiospermum sidD gene drives the synthesis of a unique extracellular, hydroxamate-type iron chelator, which is essential for fungal growth and virulence. This compound scavenges iron from pyoverdine, which might explain why S. apiospermum and Pseudomonas aeruginosa are rarely found simultaneously in the CF lungs.
Permanent Link: http://hdl.handle.net/11104/0313205