Role of the putative sit1 gene in normal germination of spores and virulence of the Mucor lusitanicus
Authors:Bernadett Vágó1,2, Kitti Bauer1,2, Naomi Varghese1,2, Sándor Kiss-Vetráb1,2, Sándor Kocsubé1,2, Mónika Varga1,2, András Szekeres1,2, Csaba Vágvölgyi1,2, Tamás Papp1,2,3,# and Gábor Nagy1,2,3,#
1 Department of Biotechnology and Microbiology, University of Szeged, Szeged, Közép fasor 52, Hungary. 2 HUN-REN-SZTE Fungal Pathomechanisms Research Group, University of Szeged, Szeged, Hungary, Szeged, Közép fasor 52, Hungary. 3 University of Szeged, Centre of Excellence for Interdisciplinary Research, Development and Innovation (SZTE IKIKK), Fungal Pathomechanisms Research Group, Szeged, Hungary, Szeged, Közép fasor 52, Hungary.
# These authors contributed equally to this work.
Keywords:
mucormycosis, siderophore, Sit1/ARN3, deferoxamine, iron acquisition.
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Conflict of interest statement:
The authors declare that they have no conflict of interests.
Please cite this article as:
Bernadett Vágó, Kitti Bauer, Naomi Varghese, Sándor Kiss-Vetráb, Sándor Kocsubé, Mónika Varga, András Szekeres, Csaba Vágvölgyi, Tamás Papp, Gábor Nagy (2025). Role of the putative sit1 gene in normal germi-nation of spores and virulence of the Mucor lusitanicus. Microbial Cell 12: 195-209. doi: 10.15698/mic2025.08.856
© 2025 Vágó et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Mucormycosis is a life-threatening infection caused by certain members of the fungal order Mucorales, with increased incidence in recent years. Individuals with untreated diabetes mellitus, and patients treated with deferoxamine are particularly susceptible to this infection. Elevated free iron concentrations in serum contribute to the development of mucormycosis. Pathogenic fungi have evolved multiple mechanisms to acquire and utilize free iron or extract it from the various iron-binding molecules within the host. The utilization of hydroxamate siderophores as xenosiderophores may contribute to the development of mucormycosis. The genome of Mucor lusitanicus encodes one Sit1 siderophore transporter. In this study, the role of the sit1 gene was characterized by generating knockout mutants using CRISPR-Cas9. Relative transcript level of the sit1 gene significantly increased in the presence of deferoxamine- and deferasirox-iron complexes. Lack of sit1 resulted in altered germination of spores and growth ability, and decreased virulence. Furthermore, absence of the gene caused elevated transcript levels of a ferric reductase (FRE), a low-affinity iron permease (FET4) and a copper dependent iron oxidase (FET3). Our result suggests that expressions of the genes involved in iron uptake affect each other. The lack of Sit1 resulted in an increased transcript level of the FRE3 gene, which may be able to reduce iron from the siderophore-iron complex. The reduced and liberated iron may be then taken up by activated FET4a. This study highlights the significance of understanding the iron acquisition mechanisms of pathogenic fungi to develop effective treatments for fungal infections.
doi: 10.15698/mic2025.08.856
Volume 12, pp. 195 to 209, published 12/08/2025.