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antioxidant agent and employs “push and pull” mechanism delivering gallium and
fetching iron which in turn renders the antimicrobial activity (Banin et al. 2008).
Complexing zirconium-89 with dessferioxamine and other bifunctional chelators
would perhaps bring related advancement in the field of bioimaging applications of
siderophores, since radionuclide-based technologies are highly specific in tracing
the molecular targets that enhance the understanding on pathophysiology in a diseased condition (Petrick et al. 2017).
9.5 Experimental Techniques
Experimental techniques in the field of studying siderophores have to be improved
a lot where Meyer et al. (2002) suggested that the techniques could be more advantageous with quick and unambiguous nature. Siderotyping is a novel characterizing
technique evolved in determining the strains according to the siderophore types
produced by them. The two different methods are analytical and biological, where
high-performance liquid chromatography (HPLC) coupled with mass spectrometry
is used mostly for analytical siderotyping and biological methods include direct
measurement of siderophore-mediated Fe in the microbial cells as well as molecular
biology methods to recognize the specific DNA sequences for siderophores (Bach
et al. 2000). Fluorescence microscopy ambient ionization mass spectrometry was
used to detect siderophores (desferrichrome, triacetylfusarinine C) in the Whitenose syndrome (WNS), suggesting their functional role in the infection and/or tissue invasion (Mascuch et al. 2015).
RP-HPLC technique has been employed for siderophore identification in
A. fumigatus which causes aspergillosis (WinkelStroker et al. 2015). However due
to lack of active uptake by the pathogen leading to signal intensification at the infection site, radiotracers were used with high specificity and sensitivity for fungal
infections (Haas et al. 2015). Molecular imaging technique has been implemented
for siderophore typing where the target was to “steal” the host iron which is tightly
sequestered by host proteins such as hemoglobin, transferrin, etc. (Haas et al. 2015).
Radiophore tagging was also employed to identify xenosiderophores by nonproducers like Saccharomyces sp. and Candida by using radiophore tagged xenosiderophore like Ga-TAFC (triacetylfusarinine C) and Ga-FOXE (ferrioxamine E) (Haas
et al. 2015). However, molecular imaging of the siderophores comes with its own
challenges where siderophore system is greatly affected in patients undergoing antifungal treatment: either the reduced iron uptake mechanisms affect the sensitivity
toward the radiotracer uptake or the patients who undergo blood transfusion suffer
from “iron overload” condition which further aids in the onset of the fungal infection (Haas et al. 2015). Hence, bioimaging technique is not effective in such cases.
The siderotyping could be widely applied in microbial diversity identification
and taxonomy (Meyer 2010) and also as chemotaxonomic marker for the identification of organism types (Bultreys et al. 2006).
9 Fungal Siderophores: Prospects and Applications
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