23
pathway can be targeted by inhibiting HMG-CoA reductase by statins class of drugs
like simvastatin and lovastatin which can interfere in the biosynthesis of siderophores.
Further, isoprenoid biosynthetic pathway and siderophore biosynthetic pathway are
interconnected by cis anhydromevalonyl-CoA which is transported across peroxisome
to cytoplasm for entering into siderophore biosynthetic pathway (Leal et al. 2013).
The potential of statins in the field of antifungal therapy has been investigated,
and it was found that these drugs have promising application, either alone or in
combination with other antifungal drugs to treat infections (Galgóczy et al. 2009;
Macreadie et al. 2006). There was also a report that antifungal activity of statins is
observed only in higher concentration. So, in order to reduce its dose, the combined
formulation of statins and azoles was tried, and these combinations show synergistic interaction. On this track, the combined dose form of lovastatin and voriconazole
was studied, and these formulations were found to be effective against various
pathogenic fungi (especially Zygomycetes) (Chamilos et al. 2006). Further, more
such combinations are under development phase for curbing the opportunistic infections caused by fungal pathogens.
2.4.3 Peptide-Based Inhibitors
Recently, research group of Balhara and coworkers identified an antifungal protein
which is called AAP (anti-Aspergillus protein) isolated from E. coli DH5α that can
be found to show antimycotic effect against pathogenic isolates of Aspergillus spp.
with a MIC in range of 5.62–31.25 μg ml
−1
. The protein was purified using anion
exchange chromatography and found to be falling in the range of 28–66 kDa after
staining with silver stain. Further, from toxicological point of view, the isolated
AAP was found to be safe for human erythrocytes at a dose 1000 μg ml
−1
(Balhara
Fig. 2.4 Sketch of
isoprenoid biosynthetic
pathway inside peroxisome
which leads to synthesis of
mevalonate
2 Inhibition of Siderophores in Blocking Fungal Infection
pathway can be targeted by inhibiting HMG-CoA reductase by statins class of drugs
like simvastatin and lovastatin which can interfere in the biosynthesis of siderophores.
Further, isoprenoid biosynthetic pathway and siderophore biosynthetic pathway are
interconnected by cis anhydromevalonyl-CoA which is transported across peroxisome
to cytoplasm for entering into siderophore biosynthetic pathway (Leal et al. 2013).
The potential of statins in the field of antifungal therapy has been investigated,
and it was found that these drugs have promising application, either alone or in
combination with other antifungal drugs to treat infections (Galgóczy et al. 2009;
Macreadie et al. 2006). There was also a report that antifungal activity of statins is
observed only in higher concentration. So, in order to reduce its dose, the combined
formulation of statins and azoles was tried, and these combinations show synergistic interaction. On this track, the combined dose form of lovastatin and voriconazole
was studied, and these formulations were found to be effective against various
pathogenic fungi (especially Zygomycetes) (Chamilos et al. 2006). Further, more
such combinations are under development phase for curbing the opportunistic infections caused by fungal pathogens.
2.4.3 Peptide-Based Inhibitors
Recently, research group of Balhara and coworkers identified an antifungal protein
which is called AAP (anti-Aspergillus protein) isolated from E. coli DH5α that can
be found to show antimycotic effect against pathogenic isolates of Aspergillus spp.
with a MIC in range of 5.62–31.25 μg ml
−1
. The protein was purified using anion
exchange chromatography and found to be falling in the range of 28–66 kDa after
staining with silver stain. Further, from toxicological point of view, the isolated
AAP was found to be safe for human erythrocytes at a dose 1000 μg ml
−1
(Balhara
Fig. 2.4 Sketch of
isoprenoid biosynthetic
pathway inside peroxisome
which leads to synthesis of
mevalonate
2 Inhibition of Siderophores in Blocking Fungal Infection