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nation, virulence or to prevent in vivo oxidative stress during infection (Blatzer
et al. 2011). The growth of C. albicans mainly depends on Fe availability. The
endothelial cell injury caused by C. albicans shows more adherence to the endothelial cell when pretreated with Fe chelators. In addition, Fe chelators upregulate the
receptors of C. albicans on the endothelial cells (Fratti et al. 1998). The studies in
the mouse model showed that N, N′, N″-triacetyl fusarinine C (TAFC) produced
within the host organism is required for fungal growth and virulence of A. fumigatus
in invasive aspergillosis. The increased TAFC concentration in the plasma is considered as an early biomarker in the invasive aspergillosis. TAFC is a cyclic tripeptide
consisting of three N 2-acetyl-N 5-cis-anhydromevalonyl-N 5-hydroxyornithine
residues linked by ester bonds. L-ornithine-N 5-monooxygenase catalyses the first
step in the biosynthesis of TAFC which causes virulence (Schrettl et al. 2004).
A. fumigatus and H. capsulatum show a severe defect in virulence when siderophore
genes are mutated or deleted. The siderophores produced by A. fumigatus can also
extract Fe from the host iron-binding protein transferrin. Tear lipocalin is a secretary
protein that inhibits the microbial growth by removing the siderophore when it is
used topically in humans (Fluckinger et al. 2004). In corneal infection caused by
Aspergillus and Fusarium, the elevated level of the siderophore binding protein and
the mutations in the siderophore production pathway leads to inhibition of fungal
growth (Hazlett et al. 2016). Thus, the siderophores are essential for the growth,
conidiation and virulence of fungus under iron-restricted condition. At the same
time, defective siderophore biosynthesis leads to decreased growth and virulence
in fungi.
12.6 Fungal Siderophores in Cancer Therapy
Fe demand is high in cancer cells to sustain the proliferation. Many studies have
been carried out to understand the role of Fe in cancer cells by modulating the genes
responsible for Fe regulation or by using siderophores. The fungal siderophores
produce their effect by the inhibition of DNA synthesis, and arrest G1-S-phase cell
cycle, attenuate Epithelial-mesenchymal transition (EMT), modify the epigenetic
signatures of malignant tumour cells and also promote the apoptosis of cancer cells.
Three natural compounds, NBRI16716A, NBRI16716B and NBRI16716C, isolated
from a fungal species, Perisporiopsis melioloides Mer-f16716, are found to be siderophores through the colour reaction to FeCl3 (Frederick et al. 1981). The compounds possessed anti- tumour activity and gave promising results on prostate cancer
(Kawada et al. 2010). Among the three compounds, NBRI16716B exhibits strong
selectivity as well as activity in vitro and NBRI16716C exhibits comparatively
weak activity.
Fe is necessary for cell proliferation and growth. It is harmful to the redox abilities of a cell because the formation of free radical may worsen the oxidative stress
and DNA damage. Fe plays an important role in tumour progression and metastasis.
Tumour-associated macrophages (TAMs) are the main source for iron. By targeting
12 A Summary on Up-To-Date Research on Fungal Siderophores on Disease…
nation, virulence or to prevent in vivo oxidative stress during infection (Blatzer
et al. 2011). The growth of C. albicans mainly depends on Fe availability. The
endothelial cell injury caused by C. albicans shows more adherence to the endothelial cell when pretreated with Fe chelators. In addition, Fe chelators upregulate the
receptors of C. albicans on the endothelial cells (Fratti et al. 1998). The studies in
the mouse model showed that N, N′, N″-triacetyl fusarinine C (TAFC) produced
within the host organism is required for fungal growth and virulence of A. fumigatus
in invasive aspergillosis. The increased TAFC concentration in the plasma is considered as an early biomarker in the invasive aspergillosis. TAFC is a cyclic tripeptide
consisting of three N 2-acetyl-N 5-cis-anhydromevalonyl-N 5-hydroxyornithine
residues linked by ester bonds. L-ornithine-N 5-monooxygenase catalyses the first
step in the biosynthesis of TAFC which causes virulence (Schrettl et al. 2004).
A. fumigatus and H. capsulatum show a severe defect in virulence when siderophore
genes are mutated or deleted. The siderophores produced by A. fumigatus can also
extract Fe from the host iron-binding protein transferrin. Tear lipocalin is a secretary
protein that inhibits the microbial growth by removing the siderophore when it is
used topically in humans (Fluckinger et al. 2004). In corneal infection caused by
Aspergillus and Fusarium, the elevated level of the siderophore binding protein and
the mutations in the siderophore production pathway leads to inhibition of fungal
growth (Hazlett et al. 2016). Thus, the siderophores are essential for the growth,
conidiation and virulence of fungus under iron-restricted condition. At the same
time, defective siderophore biosynthesis leads to decreased growth and virulence
in fungi.
12.6 Fungal Siderophores in Cancer Therapy
Fe demand is high in cancer cells to sustain the proliferation. Many studies have
been carried out to understand the role of Fe in cancer cells by modulating the genes
responsible for Fe regulation or by using siderophores. The fungal siderophores
produce their effect by the inhibition of DNA synthesis, and arrest G1-S-phase cell
cycle, attenuate Epithelial-mesenchymal transition (EMT), modify the epigenetic
signatures of malignant tumour cells and also promote the apoptosis of cancer cells.
Three natural compounds, NBRI16716A, NBRI16716B and NBRI16716C, isolated
from a fungal species, Perisporiopsis melioloides Mer-f16716, are found to be siderophores through the colour reaction to FeCl3 (Frederick et al. 1981). The compounds possessed anti- tumour activity and gave promising results on prostate cancer
(Kawada et al. 2010). Among the three compounds, NBRI16716B exhibits strong
selectivity as well as activity in vitro and NBRI16716C exhibits comparatively
weak activity.
Fe is necessary for cell proliferation and growth. It is harmful to the redox abilities of a cell because the formation of free radical may worsen the oxidative stress
and DNA damage. Fe plays an important role in tumour progression and metastasis.
Tumour-associated macrophages (TAMs) are the main source for iron. By targeting
12 A Summary on Up-To-Date Research on Fungal Siderophores on Disease…