150
combat fungal infections in human beings with reduced toxicity and side effects.
Sulochana et al. (2014) also suggested that siderophores could be benefitted as drug
in health-care issues. Carroll and Moore (2018) illustrated that the enzymes which
take part in the non-ribosomal peptide synthetase (NRPS)-independent siderophore
biosynthetic pathway are to be considered as potent anti-microbial agents. A few
reports persevered the relativity which exists between melanin biosynthesis and Fe
acquisition, as the genes involved in melanin formation (LAC1, ATX1, and CCC2)
regulate the Fe uptake (Walton et al. 2005).
Despite targeting the siderophore biosynthesis, the siderophores produced by the
fungus could be utilized as “Trojan horse” toxins by uptaking the antibiotics along
with iron inside the cells which itself affects the pathogen’s development (Ahmed
and Holmstrom 2014). The “Trojan horse” mechanisms in the treatment of iron
overload disease, thalassemia mobilizes and decreases the iron storage in the body
(Kontoghiorghe and Kontoghiorghes 2016).
Broadly, animal and plant hosts circumvent the fungal invasion using iron as a
defense component, and it is said to be “nutritional immunity” (Weinberg 2009).
Mammals encompass a strategy called hypoferremia which triggers the immunogenic signals such as IL8 production to dodge the chemical structures of strong iron
chelator produced by bacteria and fungus. With the worse condition existing in the
treatement of fungal infections, Lin et al. (2014) serendipitously discovered human
transferrin as a novel antimicrobial agent by sequestering iron and disrupting membrane potential of fungi Candida albicans (Lin et al. 2014). Few mammalian proteins called siderocalins (e.g., neutrophil gelatinase-associated lipocalin, NGAL,
and tear lipocalin, TL) interact with siderophores and lead to endocytosis and degradation (Aznar and Dellagi 2015).
The siderophore-mediated iron acquisition also assists the microbes in their survival rate within the macrophages (Nevitt and Thiele 2011). The dimorphic ascomycete Histoplasma capsulatum, the basidiomycete Cr. neoformans, the yeast-like
ascomycete C. glabrata, and the dimorphic ascomycetes Paracoccidioides brasiliensis and Blastomyces dermatitidis are capable to survive the phagocytic pathway,
despite the defense mechanism exhibited by host’s immune system (Gerwien et al.
2018). The fungus H. capsulatum maintains the intraphagosomal pH at 6.5 which
apparently inhibits phagosome function as well as iron accessibility (Hilty
et al. 2008).
Furthermore, siderophores are widely used to reduce the growth of cancerous
cells, and the relationship that exists between iron overload and cancer progression
has been reviewed thoroughly by Huang (2003). The hydroxamate desferrioxamine
reduces the tumor succession in neuroblastoma as well as induces apoptosis in
malignant melanoma cells (Schrettl et al. 2010).
Diagnosis is a crucial technique where a lot has to be improved to determine the
accurate localization, characterization, and risky stages at the earliest of a diseased
condition which would influence the success rate of the therapy. Molecular imaging
techniques such as radiological, optical diagnosis in the clinical practice are capable
of identifying the infections, but however have some limitations over specificity.
Dessferioxamine in complex with nonradioactive gallium was designed as an
S. Manoharan et al.
combat fungal infections in human beings with reduced toxicity and side effects.
Sulochana et al. (2014) also suggested that siderophores could be benefitted as drug
in health-care issues. Carroll and Moore (2018) illustrated that the enzymes which
take part in the non-ribosomal peptide synthetase (NRPS)-independent siderophore
biosynthetic pathway are to be considered as potent anti-microbial agents. A few
reports persevered the relativity which exists between melanin biosynthesis and Fe
acquisition, as the genes involved in melanin formation (LAC1, ATX1, and CCC2)
regulate the Fe uptake (Walton et al. 2005).
Despite targeting the siderophore biosynthesis, the siderophores produced by the
fungus could be utilized as “Trojan horse” toxins by uptaking the antibiotics along
with iron inside the cells which itself affects the pathogen’s development (Ahmed
and Holmstrom 2014). The “Trojan horse” mechanisms in the treatment of iron
overload disease, thalassemia mobilizes and decreases the iron storage in the body
(Kontoghiorghe and Kontoghiorghes 2016).
Broadly, animal and plant hosts circumvent the fungal invasion using iron as a
defense component, and it is said to be “nutritional immunity” (Weinberg 2009).
Mammals encompass a strategy called hypoferremia which triggers the immunogenic signals such as IL8 production to dodge the chemical structures of strong iron
chelator produced by bacteria and fungus. With the worse condition existing in the
treatement of fungal infections, Lin et al. (2014) serendipitously discovered human
transferrin as a novel antimicrobial agent by sequestering iron and disrupting membrane potential of fungi Candida albicans (Lin et al. 2014). Few mammalian proteins called siderocalins (e.g., neutrophil gelatinase-associated lipocalin, NGAL,
and tear lipocalin, TL) interact with siderophores and lead to endocytosis and degradation (Aznar and Dellagi 2015).
The siderophore-mediated iron acquisition also assists the microbes in their survival rate within the macrophages (Nevitt and Thiele 2011). The dimorphic ascomycete Histoplasma capsulatum, the basidiomycete Cr. neoformans, the yeast-like
ascomycete C. glabrata, and the dimorphic ascomycetes Paracoccidioides brasiliensis and Blastomyces dermatitidis are capable to survive the phagocytic pathway,
despite the defense mechanism exhibited by host’s immune system (Gerwien et al.
2018). The fungus H. capsulatum maintains the intraphagosomal pH at 6.5 which
apparently inhibits phagosome function as well as iron accessibility (Hilty
et al. 2008).
Furthermore, siderophores are widely used to reduce the growth of cancerous
cells, and the relationship that exists between iron overload and cancer progression
has been reviewed thoroughly by Huang (2003). The hydroxamate desferrioxamine
reduces the tumor succession in neuroblastoma as well as induces apoptosis in
malignant melanoma cells (Schrettl et al. 2010).
Diagnosis is a crucial technique where a lot has to be improved to determine the
accurate localization, characterization, and risky stages at the earliest of a diseased
condition which would influence the success rate of the therapy. Molecular imaging
techniques such as radiological, optical diagnosis in the clinical practice are capable
of identifying the infections, but however have some limitations over specificity.
Dessferioxamine in complex with nonradioactive gallium was designed as an
S. Manoharan et al.