314
12.4.5 Myxobacteria
Myxobacteria are a group of proteobacteria that predominantly inhabit the soil and
are characterized by the ability to sporulate within fruiting bodies. They are social
microbes with the ability to form cellular associations that form swarms that move
by axonal cellular motion called gliding. Such ripple-like movement is used to
accumulate particulate organic matter they feed on. When these waves of myxobacterium collide, they form cellular aggregates that can accommodate up to 10
5
cells
and form fruiting bodies. Cells within these aggregates form myxospores that germinate when nutrients are available. Events like sporulation and germination are
regulated by intracellular and extracellular signaling mediated by proteins and small
metabolites.
12.4.5.1 Antimicrobials from Myxobacteria
The myxobacterial metabolome is rich in diverse and biologically active metabolites (Schäberle et al. 2014). Up to 40% of biologically active metabolites described
from myxobacteria represent novel structural classes of antimicrobials. They form
nonglycosylated metabolites unlike actinomycetes and inhibit novel and unique targets. The diversity and novelty in the bioactives produced by myxobacteria have
been argued to confer competitive advantage in the soil ecosystem, which enable
effective cell–cell communication in population and in predation.
12.4.5.2 Inhibitors of Bacterial RNA Polymerases
DNA-dependent RNA polymerases are well-known targets for antimicrobials. They
are essential for the survival of bacteria and are highly conserved. Four antimicrobials and their derivatives with the ability to inhibit bacterial RNA polymerase are
identified from myxobacteria namely corallopyronin A, myxopyronin A, ripostatin
A and sorangicin A. Corallopyronins are produced by a strain of Corallococcus
coralloides. They contain a core pyrone ring attached to two conformationally flexible chains called the western and eastern chains. The western chain is lipophilic
with three methyl groups, a hydroxyl group and a diene element. The eastern chain
contains one methyl group, an enamide functional group and a carbamate moiety.
Three analogues, namely, carollopyronin A (Fig. 12.8a), B and C are also known.
Myxopyronin A and B are antibiotics that are structurally similar to carollopyronin
isolated form Myxococcus fulvus strain. Myxopyronin A and Myxopyronin B share
the pyrone ring and western chains of carollopyronin but have a shorter and unhydroxylated eastern ring terminated at carbon C-24 and carbon C-25 of corallopyronins, respectively. Carollopyronin A shows antimicrobial activity against S. aureus
and Bacillus meagaterium. Other carollopyronins show weak activity against these
organisms. Carollopyronin A shows weak activity against Mycobacterium smegmatis and relatively better activity against M. bovis. Carollopyronin A is also active
in vivo against Wolbachia species, intracellular bacteria of nematodes. This offers
the possibility of developing a drug for filariasis without the risk of developing
cross-resistance to mycobacterium. Myxopyronins shows activity against S. aureus
D. Francis
12.4.5 Myxobacteria
Myxobacteria are a group of proteobacteria that predominantly inhabit the soil and
are characterized by the ability to sporulate within fruiting bodies. They are social
microbes with the ability to form cellular associations that form swarms that move
by axonal cellular motion called gliding. Such ripple-like movement is used to
accumulate particulate organic matter they feed on. When these waves of myxobacterium collide, they form cellular aggregates that can accommodate up to 10
5
cells
and form fruiting bodies. Cells within these aggregates form myxospores that germinate when nutrients are available. Events like sporulation and germination are
regulated by intracellular and extracellular signaling mediated by proteins and small
metabolites.
12.4.5.1 Antimicrobials from Myxobacteria
The myxobacterial metabolome is rich in diverse and biologically active metabolites (Schäberle et al. 2014). Up to 40% of biologically active metabolites described
from myxobacteria represent novel structural classes of antimicrobials. They form
nonglycosylated metabolites unlike actinomycetes and inhibit novel and unique targets. The diversity and novelty in the bioactives produced by myxobacteria have
been argued to confer competitive advantage in the soil ecosystem, which enable
effective cell–cell communication in population and in predation.
12.4.5.2 Inhibitors of Bacterial RNA Polymerases
DNA-dependent RNA polymerases are well-known targets for antimicrobials. They
are essential for the survival of bacteria and are highly conserved. Four antimicrobials and their derivatives with the ability to inhibit bacterial RNA polymerase are
identified from myxobacteria namely corallopyronin A, myxopyronin A, ripostatin
A and sorangicin A. Corallopyronins are produced by a strain of Corallococcus
coralloides. They contain a core pyrone ring attached to two conformationally flexible chains called the western and eastern chains. The western chain is lipophilic
with three methyl groups, a hydroxyl group and a diene element. The eastern chain
contains one methyl group, an enamide functional group and a carbamate moiety.
Three analogues, namely, carollopyronin A (Fig. 12.8a), B and C are also known.
Myxopyronin A and B are antibiotics that are structurally similar to carollopyronin
isolated form Myxococcus fulvus strain. Myxopyronin A and Myxopyronin B share
the pyrone ring and western chains of carollopyronin but have a shorter and unhydroxylated eastern ring terminated at carbon C-24 and carbon C-25 of corallopyronins, respectively. Carollopyronin A shows antimicrobial activity against S. aureus
and Bacillus meagaterium. Other carollopyronins show weak activity against these
organisms. Carollopyronin A shows weak activity against Mycobacterium smegmatis and relatively better activity against M. bovis. Carollopyronin A is also active
in vivo against Wolbachia species, intracellular bacteria of nematodes. This offers
the possibility of developing a drug for filariasis without the risk of developing
cross-resistance to mycobacterium. Myxopyronins shows activity against S. aureus
D. Francis