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11.1 Introduction
Like bacteria and viruses, fungi also infect human beings and results in fungal diseases, also known as mycoses. Though millions of fungal species exist in nature,
only few are harmful (Cdc.gov 2017). In humans, fungi generally reside in the skin,
lungs and blood stream. Fungal infections in the skin are usually mild in nature and
are observed as skin rashes. Fungal infections in lungs are similar to other lung
infections such as a flu and tuberculosis. When fungus enters into the blood stream,
it causes systemic fungal infections which are less common but life threatening, as
they are associated with a higher mortality rate (Mavor et al. 2005). Aspergillosis,
candidiasis, coccidioidomycosis (valley fever), blastomycosis, talaromycosis, sporotrichosis, histoplasmosis, ringworm, fungal eye infections and fungal skin infections are notable human fungal infections (Cdc.gov 2017).
Fungal infections are generally treated by antifungal drugs either as topical
applications or given orally (Hay 2018). Clotrimazole, Ketoconazole, Miconazole,
Oxiconazole, Sulconazole, Terbinafine, Terconazole, Tioconazole and Tolnaftate
are few such drugs available to treat fungal diseases (Campoy and Adrio 2017).
Despite the existence of many antifungal agents, fungal diseases are more common
than previously realized. In addition, the newly emerging fungi are becoming
increasingly problematic. A few fungal infections are life threatening, if they are not
identified and treated in their initial stage itself (Cdc.gov 2017). Furthermore, recent
outbreaks such as histoplasmosis in Illinois in 2013 and in the Dominican Republic
in 2015, the fatal gastrointestinal mucormycosis in a premature infant in 2014, coccidioidomycosis (Valley fever) in California’s Central Valley in 2013, fungal meningitis and other fungal infections associated with contaminated steroid injections in
2012, endophthalmitis in 2012, mucormycosis in 2011, blastomycosis in 2010–2011
(Cdc.gov 2017) insist on the need and importance of designing newer and more
efficient antifungal agents.
Identifying and validating a potential drug target is a crucial step in drug discovery, as it determines the success of any drug designing process. Hence, it is essential
to understand the existing drugs, its drug target, their mechanism of action and
drawbacks before going to find novel drug targets for antifungal drug discovery. The
current antifungal drugs primarily target and inhibit the enzymes involved in the
biosynthetic pathways such as cell wall, cell membrane and DNA. In addition, the
antifungal agents also target the essential components of the fungal cell wall such as
ergosterol, lanosterol, chitin, glucans and several glycoproteins and inhibit them.
Few antifungal agents disrupt mitotic spindles and inhibit fungal mitosis (Mazu
et al. 2016). However, the current antifungal agents are associated with drawbacks
such as: allergic reactions in humans; adverse reactions like altered oestrogen level
and liver damage (Kyriakidis et al. 2017); significant side effects (HSE.ie 2019);
association with many drug interactions (Doctor Fungus 2019); and the emergence
of drug resistant and multidrug resistant strains (Cdc.gov 2019a, b). Hence, in order
to overcome these obstacles, in recent years, much focus has been redirected towards
siderophores, one of the most potent drug targets in bacteria and fungi (Balhara
A. Shanmugam et al.
11.1 Introduction
Like bacteria and viruses, fungi also infect human beings and results in fungal diseases, also known as mycoses. Though millions of fungal species exist in nature,
only few are harmful (Cdc.gov 2017). In humans, fungi generally reside in the skin,
lungs and blood stream. Fungal infections in the skin are usually mild in nature and
are observed as skin rashes. Fungal infections in lungs are similar to other lung
infections such as a flu and tuberculosis. When fungus enters into the blood stream,
it causes systemic fungal infections which are less common but life threatening, as
they are associated with a higher mortality rate (Mavor et al. 2005). Aspergillosis,
candidiasis, coccidioidomycosis (valley fever), blastomycosis, talaromycosis, sporotrichosis, histoplasmosis, ringworm, fungal eye infections and fungal skin infections are notable human fungal infections (Cdc.gov 2017).
Fungal infections are generally treated by antifungal drugs either as topical
applications or given orally (Hay 2018). Clotrimazole, Ketoconazole, Miconazole,
Oxiconazole, Sulconazole, Terbinafine, Terconazole, Tioconazole and Tolnaftate
are few such drugs available to treat fungal diseases (Campoy and Adrio 2017).
Despite the existence of many antifungal agents, fungal diseases are more common
than previously realized. In addition, the newly emerging fungi are becoming
increasingly problematic. A few fungal infections are life threatening, if they are not
identified and treated in their initial stage itself (Cdc.gov 2017). Furthermore, recent
outbreaks such as histoplasmosis in Illinois in 2013 and in the Dominican Republic
in 2015, the fatal gastrointestinal mucormycosis in a premature infant in 2014, coccidioidomycosis (Valley fever) in California’s Central Valley in 2013, fungal meningitis and other fungal infections associated with contaminated steroid injections in
2012, endophthalmitis in 2012, mucormycosis in 2011, blastomycosis in 2010–2011
(Cdc.gov 2017) insist on the need and importance of designing newer and more
efficient antifungal agents.
Identifying and validating a potential drug target is a crucial step in drug discovery, as it determines the success of any drug designing process. Hence, it is essential
to understand the existing drugs, its drug target, their mechanism of action and
drawbacks before going to find novel drug targets for antifungal drug discovery. The
current antifungal drugs primarily target and inhibit the enzymes involved in the
biosynthetic pathways such as cell wall, cell membrane and DNA. In addition, the
antifungal agents also target the essential components of the fungal cell wall such as
ergosterol, lanosterol, chitin, glucans and several glycoproteins and inhibit them.
Few antifungal agents disrupt mitotic spindles and inhibit fungal mitosis (Mazu
et al. 2016). However, the current antifungal agents are associated with drawbacks
such as: allergic reactions in humans; adverse reactions like altered oestrogen level
and liver damage (Kyriakidis et al. 2017); significant side effects (HSE.ie 2019);
association with many drug interactions (Doctor Fungus 2019); and the emergence
of drug resistant and multidrug resistant strains (Cdc.gov 2019a, b). Hence, in order
to overcome these obstacles, in recent years, much focus has been redirected towards
siderophores, one of the most potent drug targets in bacteria and fungi (Balhara
A. Shanmugam et al.