321
of activity and generally act by inhibition of cell wall synthesis. Cephalosporins are
a subgroup of β-lactam antibiotics with structural and functional similarity to penicillins. The first cephalosporin antibiotic was discovered from Cephalosporium
acremonium, saprotrophic fungi found in soil, plant debris and decaying mushrooms. The natural cephalosporin was then modified chemically to produce the
modern-day versions of the antibiotic.
12.4.6.3 Antifungal Antibiotics
Griseofulvin (Fig. 12.9a) is an orally administered antifungal agent isolated from
the fungus Penicillium griseofulvum. Griseofulvin is used to treat fungal dermatological infections in humans. It is a fungistatic agent that disrupts the mitotic spindle
in fungal cells to arrest them in metaphase of the cell cycle. Strobilurins are a group
of agricultural fungicides derived from natural fungicidal derivatives of β-methoxy
acrylic acid produced by a range of basidiomycete wood-rotting fungi (Balba 2007).
Strobilurin A (Fig. 12.9b) and Oudemanzin A are produced by Strobilurus tenacellus and Oudemansiella mucida respectively. They are respiratory inhibitors that act
by inhibiting mitochondrial respiration by binding to cytochrome b. This binding
prevents the electron transfer between cyctochrome b and cytochrome c1 and prevents the fungal cell from producing ATP. These naturally occurring molecules were
modified to produce commercially used strobilurins including azoxystrobin, the
world’s largest agricultural fungicidal agent.
Echinocandins are a class of antifungal drugs that act by the inhibition of β-D
glucans in the fungal cell wall. They are characterized by low toxicity and a wide
antifungal spectrum including most isolates of Candida spp., Aspergillus spp. and
Pneumocystis carinii. The first commercially licensed echinocandin is caspofungin
acetate sold by Merck. Inc. under the trade name Cancidas for the treatment of invasive aspergillosis. Echinocandins are chemically modified lipopeptides originally
obtained from fermentation broths of various fungi. Aculeasin A was isolated from
Aspergillus aculeatus, echinocandin B (Fig. 12.9c) from Aspergillus rugulovalvus,
pneumocandin B from Zalerion arboricola, enfumafungin from a hormonema-like
fungus and the papulacandin from Papularia sphaerosperma. Sordarins are derivatives of sordarin (Fig. 12.9d), originally isolated from fermentation broths of terrestrial ascomycete Sordaria araneosa. They are recognized as potential antifungal
agents with a broad spectrum of activity against many fungal pathogens infecting
immune-compromised individuals. They are active against Candida spp.,
Cryptococcus neoformans, Pneumocystis carinii, as well as dermatophytes. These
molecules exert their activity by inhibiting the elongation step of bacterial protein
synthesis in the target fungi (Liang 2008). This mechanism of action is unique
among typical antifungal agents that act by inhibiting cell wall biosynthesis.
12.4.6.4 Alkaloids and Polyketides
Ergot alkaloids are mycotoxins produced by the genus Claviceps belonging to the
phylum ascomycota. Two alkaloids belonging to this group, agroclavine (Fig. 12.9e)
and festuclavine, show bacteriostatic activity against E. coli, S. aureus, P. aeurogenosa and other bacteria (Matuschek et al. 2011). Diketopiperazine alkaloids are
12 Antimicrobials from Microbes
of activity and generally act by inhibition of cell wall synthesis. Cephalosporins are
a subgroup of β-lactam antibiotics with structural and functional similarity to penicillins. The first cephalosporin antibiotic was discovered from Cephalosporium
acremonium, saprotrophic fungi found in soil, plant debris and decaying mushrooms. The natural cephalosporin was then modified chemically to produce the
modern-day versions of the antibiotic.
12.4.6.3 Antifungal Antibiotics
Griseofulvin (Fig. 12.9a) is an orally administered antifungal agent isolated from
the fungus Penicillium griseofulvum. Griseofulvin is used to treat fungal dermatological infections in humans. It is a fungistatic agent that disrupts the mitotic spindle
in fungal cells to arrest them in metaphase of the cell cycle. Strobilurins are a group
of agricultural fungicides derived from natural fungicidal derivatives of β-methoxy
acrylic acid produced by a range of basidiomycete wood-rotting fungi (Balba 2007).
Strobilurin A (Fig. 12.9b) and Oudemanzin A are produced by Strobilurus tenacellus and Oudemansiella mucida respectively. They are respiratory inhibitors that act
by inhibiting mitochondrial respiration by binding to cytochrome b. This binding
prevents the electron transfer between cyctochrome b and cytochrome c1 and prevents the fungal cell from producing ATP. These naturally occurring molecules were
modified to produce commercially used strobilurins including azoxystrobin, the
world’s largest agricultural fungicidal agent.
Echinocandins are a class of antifungal drugs that act by the inhibition of β-D
glucans in the fungal cell wall. They are characterized by low toxicity and a wide
antifungal spectrum including most isolates of Candida spp., Aspergillus spp. and
Pneumocystis carinii. The first commercially licensed echinocandin is caspofungin
acetate sold by Merck. Inc. under the trade name Cancidas for the treatment of invasive aspergillosis. Echinocandins are chemically modified lipopeptides originally
obtained from fermentation broths of various fungi. Aculeasin A was isolated from
Aspergillus aculeatus, echinocandin B (Fig. 12.9c) from Aspergillus rugulovalvus,
pneumocandin B from Zalerion arboricola, enfumafungin from a hormonema-like
fungus and the papulacandin from Papularia sphaerosperma. Sordarins are derivatives of sordarin (Fig. 12.9d), originally isolated from fermentation broths of terrestrial ascomycete Sordaria araneosa. They are recognized as potential antifungal
agents with a broad spectrum of activity against many fungal pathogens infecting
immune-compromised individuals. They are active against Candida spp.,
Cryptococcus neoformans, Pneumocystis carinii, as well as dermatophytes. These
molecules exert their activity by inhibiting the elongation step of bacterial protein
synthesis in the target fungi (Liang 2008). This mechanism of action is unique
among typical antifungal agents that act by inhibiting cell wall biosynthesis.
12.4.6.4 Alkaloids and Polyketides
Ergot alkaloids are mycotoxins produced by the genus Claviceps belonging to the
phylum ascomycota. Two alkaloids belonging to this group, agroclavine (Fig. 12.9e)
and festuclavine, show bacteriostatic activity against E. coli, S. aureus, P. aeurogenosa and other bacteria (Matuschek et al. 2011). Diketopiperazine alkaloids are
12 Antimicrobials from Microbes