179
11.2.5 Acidification and Mobilization
C. albicans and C. neoformans use an acidification process to acquire iron from the
host (Almeida et al. 2009). They grow anaerobically and acidify their medium. In
an acidic environment, the iron accumulates at the cell surface and is transported
into the cell with the help of the excreted hydroxy acids (Howard 1999).
11.3 Siderophore-Mediated Iron Transport
The siderophore-mediated iron transport is an energy-dependent process and this
transport process usually depends on the nature and type of siderophore, metal-ion
coordination geometry and N-acyl residues surrounding the metal centre. Four different mechanism are associated with this siderophore-mediated iron uptake in
fungi (Howard 1999; Renshaw et al. 2002). They are as follows:
1. Shuttle mechanism
2. Taxicab mechanism
3. Hydrolytic mechanism
4. Reductive mechanism
11.3.1 Shuttle Mechanism
In the shuttle mechanism, the entire siderophore-iron complex is transported into
the cell. After the entire complex is moved into the cell, the iron is released and free
siderophore is then excreted.
11.3.2 Taxicab Mechanism
In this mechanism, the iron from extracellular siderophores is transferred into intracellular ligands. Here, only the iron moves across the cell membrane and not the
extracellular siderophores.
11.3.3 Hydrolytic Mechanism
In this transport, the entire siderophore-iron complex is transported into the cell and
inside the cell by simultaneous action of reductase and esterases, and the iron is
released.
11 Siderophores in Antifungal Drug Discovery: A Computational Approach
11.2.5 Acidification and Mobilization
C. albicans and C. neoformans use an acidification process to acquire iron from the
host (Almeida et al. 2009). They grow anaerobically and acidify their medium. In
an acidic environment, the iron accumulates at the cell surface and is transported
into the cell with the help of the excreted hydroxy acids (Howard 1999).
11.3 Siderophore-Mediated Iron Transport
The siderophore-mediated iron transport is an energy-dependent process and this
transport process usually depends on the nature and type of siderophore, metal-ion
coordination geometry and N-acyl residues surrounding the metal centre. Four different mechanism are associated with this siderophore-mediated iron uptake in
fungi (Howard 1999; Renshaw et al. 2002). They are as follows:
1. Shuttle mechanism
2. Taxicab mechanism
3. Hydrolytic mechanism
4. Reductive mechanism
11.3.1 Shuttle Mechanism
In the shuttle mechanism, the entire siderophore-iron complex is transported into
the cell. After the entire complex is moved into the cell, the iron is released and free
siderophore is then excreted.
11.3.2 Taxicab Mechanism
In this mechanism, the iron from extracellular siderophores is transferred into intracellular ligands. Here, only the iron moves across the cell membrane and not the
extracellular siderophores.
11.3.3 Hydrolytic Mechanism
In this transport, the entire siderophore-iron complex is transported into the cell and
inside the cell by simultaneous action of reductase and esterases, and the iron is
released.
11 Siderophores in Antifungal Drug Discovery: A Computational Approach