43
monooxygenase SidA (Olucha et al. 2011). Second step involves the splitting of
extracellular and intracellular siderophores. Extracellular siderophores are produced by transferring the anhydromevalonyl to N5-hydroxyornithine using transacylase SidF (Schrettl et al. 2007). This is produced by CoA ligation and dehydration
catalyzed by SidI and SidH, respectively (Yasmin et al. 2011). FC biosynthesis
involves two transacetylases such as SidL and an unknown enzyme that is upregulated by the starvation of iron. The assembly of FsC and FC is catalyzed by two
NRPS such as SidD and SidC. Later, SidG catalyzes N2-acetylation of FsC for
forming TAFC.
The extracellular and non-extracellular siderophores are vital for growth during
iron limitation (ΔsidA mutant) in A. fumigatus and A. nidulans (Eisendle et al.
2003; Schrettl et al. 2004). Hence, the removal of siderophore biosynthesis leads to
complete a virulence of A. fumigatus in murine model of aspergillosis. The lack in
either extracellular (ΔsidI, ΔsidH, ΔsidF, or ΔsidD mutants) or intracellular siderophores (ΔsidC mutants) leads to partial attenuation of virulence (Schrettl et al.
2007; Yasmin et al. 2011). Biosynthetic pathways of fungal siderophores thus provide the potential targets for novel and selective therapy.
3.4 Diagnosis of Aspergillosis
Diagnosis of Aspergilloma is quite and difficult process, as Aspergillus species are
commonly found in environment it is difficult to differentiate from other molds
under microscopic examination (Ruhnke et al. 2003). Mycological investigation
and diagnosis of invasive aspergillosis is difficult with the low diagnostic yield and
sensitivity of the cultures particularly from lower respiratory secretions (Tarrand
et al. 2003; Mennink-Kersten et al. 2004). Blood test may be preferred to diagnose
people under early stage of invasive aspergillosis with weakened immune systems.
Diagnosis is mainly by clinical experiments and aided with imaging techniques –
computerized tomography (CT) scan, respiratory secretion (sputum) test, tissue and
blood test, and biopsy (Nalesnik et al. 1980; Patterson et al. 1986; Kuhlman et al.
1987). Recently highly specific antibody- guided imaging technologies have been
described for the in vivo diagnosis of fungal diseases in animal models, with high
quality for translation to human disease diagnosis (Rolle et al. 2016).
Clinical diagnosis of invasive pulmonary aspergillosis (IPA) remains tremendously difficult, due to the fact that patients remain with nonspecific symptoms, and
also does not have responsive biomarker activity during diagnostic procedures.
Radiographic imaging of the lungs of the affected individual is the commonly used
diagnostic method in these invasive fungal infections. Their regularity determined
in chest CT report may reflect the presence of IPA, but it is not sufficient for complete diagnosis of this fungal disease (Nucci et al. 2010).
In case of Aspergillus sinusitis, fungal cultures are required to diagnose the
infection accurately. Particularly fungi do not give fine stain with route stains, so the
specially synthesized silver-impregnated fungal stains (Gomori methenamine
3 Association of Fungal Siderophores in Human Diseases: Roles and Treatments
monooxygenase SidA (Olucha et al. 2011). Second step involves the splitting of
extracellular and intracellular siderophores. Extracellular siderophores are produced by transferring the anhydromevalonyl to N5-hydroxyornithine using transacylase SidF (Schrettl et al. 2007). This is produced by CoA ligation and dehydration
catalyzed by SidI and SidH, respectively (Yasmin et al. 2011). FC biosynthesis
involves two transacetylases such as SidL and an unknown enzyme that is upregulated by the starvation of iron. The assembly of FsC and FC is catalyzed by two
NRPS such as SidD and SidC. Later, SidG catalyzes N2-acetylation of FsC for
forming TAFC.
The extracellular and non-extracellular siderophores are vital for growth during
iron limitation (ΔsidA mutant) in A. fumigatus and A. nidulans (Eisendle et al.
2003; Schrettl et al. 2004). Hence, the removal of siderophore biosynthesis leads to
complete a virulence of A. fumigatus in murine model of aspergillosis. The lack in
either extracellular (ΔsidI, ΔsidH, ΔsidF, or ΔsidD mutants) or intracellular siderophores (ΔsidC mutants) leads to partial attenuation of virulence (Schrettl et al.
2007; Yasmin et al. 2011). Biosynthetic pathways of fungal siderophores thus provide the potential targets for novel and selective therapy.
3.4 Diagnosis of Aspergillosis
Diagnosis of Aspergilloma is quite and difficult process, as Aspergillus species are
commonly found in environment it is difficult to differentiate from other molds
under microscopic examination (Ruhnke et al. 2003). Mycological investigation
and diagnosis of invasive aspergillosis is difficult with the low diagnostic yield and
sensitivity of the cultures particularly from lower respiratory secretions (Tarrand
et al. 2003; Mennink-Kersten et al. 2004). Blood test may be preferred to diagnose
people under early stage of invasive aspergillosis with weakened immune systems.
Diagnosis is mainly by clinical experiments and aided with imaging techniques –
computerized tomography (CT) scan, respiratory secretion (sputum) test, tissue and
blood test, and biopsy (Nalesnik et al. 1980; Patterson et al. 1986; Kuhlman et al.
1987). Recently highly specific antibody- guided imaging technologies have been
described for the in vivo diagnosis of fungal diseases in animal models, with high
quality for translation to human disease diagnosis (Rolle et al. 2016).
Clinical diagnosis of invasive pulmonary aspergillosis (IPA) remains tremendously difficult, due to the fact that patients remain with nonspecific symptoms, and
also does not have responsive biomarker activity during diagnostic procedures.
Radiographic imaging of the lungs of the affected individual is the commonly used
diagnostic method in these invasive fungal infections. Their regularity determined
in chest CT report may reflect the presence of IPA, but it is not sufficient for complete diagnosis of this fungal disease (Nucci et al. 2010).
In case of Aspergillus sinusitis, fungal cultures are required to diagnose the
infection accurately. Particularly fungi do not give fine stain with route stains, so the
specially synthesized silver-impregnated fungal stains (Gomori methenamine
3 Association of Fungal Siderophores in Human Diseases: Roles and Treatments