180
11.3.4 Reductive Mechanism
In a reductive transport, the complex is not transported into the cell. Instead, the
reduction takes place in the membrane and the reduced iron is taken into the cell.
11.4 Siderophore-Mediated Iron Storage
Iron is required by almost all living organisms for survival. Iron acquisition, uptake
and storage are essential not only for surveillance and these also determine the virulence of an organism. Iron assimilation involves the conversion of insoluble ferric to
ferrous iron by means of reduction or chelation. The unused internalized iron may
generate free radicals, re-polymerize and become toxic. In order to avoid this,
proper storage of iron is necessary. Various iron storage mechanisms are found in
different organisms. In general, fungi use three iron storage mechanisms. They are
(i) usage of iron storage protein like mycoprotein, (ii) vacuolar iron storage and (iii)
siderophore-mediated iron storage (Garnerin et al. 2017).
Certain types of iron-rich proteins are found in the members of Zygomycota.
They are mycoferritin and zygoferritin (a special type of ferritin found only in
Zygomycetes) and are used as iron storage compounds. However, the phyla
Ascomycota and Basidiomycota do not produce this kind of protein.
The vacuolar- and siderophore-mediated iron storage mechanisms are observed
in most of the fungi. In S. cerevisiae, iron (Fe
3+
) bound with polyphosphates are
stored in vacuoles. N. Crassa, a widely studied member of the family of Ascomycota,
produce two major hydroxamate-type siderophores coprogen and ferrichrocin.
Among these, the (intracellular) ferrichrocin acts as an iron storage compound. In
ascomycetes and basidiomycetes, hydroxamate-type siderophores act as iron storage molecules (Howard 1999).
11.5 Drug Discovery Strategies
Microbial siderophores not only function as chelating agents for minerals, especially iron, they also act as virulent factors (Haas et al. 2008). Hence, targeting
microbial siderophores is one of the best options in overcoming the fungal infections as well as protecting humans from their virulent power. There are many ways
by which siderophores can be targeted while designing a new drug. This includes
targeting siderophore-biosynthetic pathways by inhibiting the catalytic enzymes
involved in these pathways; targeting siderophore transport mechanisms; targeting
siderophore-mediated iron storage; targeting iron acquisition mechanisms; conjugating the drugs with siderophores; and synthesizing siderophore analogues
or mimics.
A. Shanmugam et al.
11.3.4 Reductive Mechanism
In a reductive transport, the complex is not transported into the cell. Instead, the
reduction takes place in the membrane and the reduced iron is taken into the cell.
11.4 Siderophore-Mediated Iron Storage
Iron is required by almost all living organisms for survival. Iron acquisition, uptake
and storage are essential not only for surveillance and these also determine the virulence of an organism. Iron assimilation involves the conversion of insoluble ferric to
ferrous iron by means of reduction or chelation. The unused internalized iron may
generate free radicals, re-polymerize and become toxic. In order to avoid this,
proper storage of iron is necessary. Various iron storage mechanisms are found in
different organisms. In general, fungi use three iron storage mechanisms. They are
(i) usage of iron storage protein like mycoprotein, (ii) vacuolar iron storage and (iii)
siderophore-mediated iron storage (Garnerin et al. 2017).
Certain types of iron-rich proteins are found in the members of Zygomycota.
They are mycoferritin and zygoferritin (a special type of ferritin found only in
Zygomycetes) and are used as iron storage compounds. However, the phyla
Ascomycota and Basidiomycota do not produce this kind of protein.
The vacuolar- and siderophore-mediated iron storage mechanisms are observed
in most of the fungi. In S. cerevisiae, iron (Fe
3+
) bound with polyphosphates are
stored in vacuoles. N. Crassa, a widely studied member of the family of Ascomycota,
produce two major hydroxamate-type siderophores coprogen and ferrichrocin.
Among these, the (intracellular) ferrichrocin acts as an iron storage compound. In
ascomycetes and basidiomycetes, hydroxamate-type siderophores act as iron storage molecules (Howard 1999).
11.5 Drug Discovery Strategies
Microbial siderophores not only function as chelating agents for minerals, especially iron, they also act as virulent factors (Haas et al. 2008). Hence, targeting
microbial siderophores is one of the best options in overcoming the fungal infections as well as protecting humans from their virulent power. There are many ways
by which siderophores can be targeted while designing a new drug. This includes
targeting siderophore-biosynthetic pathways by inhibiting the catalytic enzymes
involved in these pathways; targeting siderophore transport mechanisms; targeting
siderophore-mediated iron storage; targeting iron acquisition mechanisms; conjugating the drugs with siderophores; and synthesizing siderophore analogues
or mimics.
A. Shanmugam et al.