317
12.4.5.4 Inhibitors of Respiration
Three metabolites of the isoprenoid quinoline alkaloid group, namely, aurachin A
(Fig. 12.8d), B and C are produced by Stigmatella aurantiaca and members of
Rhodococcus species. Aurachins D and E are also isolated as minor products. All
aurachins share the quinoline nucleus substituted with a sesquiterpene. Aurachins
show a narrow spectrum of activity directed toward gram-positive bacteria and have
no effect on gram-negative bacteria. Aurachins also exhibit antiplasmodial activity
by inhibiting Plasmodium falsiparum in vitro. They show weak antifungal activity
against fungi like Debaryomyces hansenii and Saccharomyces cerevisiae. They
share structural similarities with the respiratory chain inhibitor 2-heptyl-4hydroxyquinoline-N-oxide (HQNO) and is able to prevent NADPH oxidation at
very low concentrations compared to HQNO.
Thuggacins are a group of macrolides containing a thiazol group produced by
Sorangium cellulosum strain So ce895. Four thuggacins are identified and named as
thuggacin A, B, C and methyl thuggacin A. In addition to the thiazole ring, thuggacins contain a diene moiety, an α, β unsaturated lactone with an n-hexyl side chain
attached at C-2 and an additional side chain at C-16 containing three hydroxyl and
a diene function. More thuggacins were isolated later from Chondromyces crocatus
strain Cm c5. Thuggacins exhibit antibacterial activity against gram-positive bacteria, including Micrococcus luteus. They also show activity against mycobacteria
like M. luteus, M. phlei, M. chitae and M. tuberculosis. Thuggacins bring about their
antibiotic effects by inhibiting the terminal stages of respiration thereby cutting
down the energy supply to the target cells (Steinmetz et al. 2007).
12.4.5.5 Inhibitors of Biofilm Formation
Biofilms offer increased resistance to antibiotics compared to free-living bacteria
because of the impermeable barrier created by biofilms to antibiotic penetration.
The search of antimicrobials that can disrupt biofilm structures is active. Carolacton
(Fig. 12.8e) is a macrolide antibiotic isolated from Sporangium cellulosum strain So
ce960 that show biofilm disruptive activity. The structure contains a 12-membered
lactone ring with two secondary hydroxyl groups at C-17 and C-18 and a terminal
carboxyl group on the side chain. Carolacton shows inhibitory activity against the
gram-negative bacterial strain E. coli tolC along with a disruptive action on bacterial biofilms. It showed promising activity against the formation of dental caries and
endocarditis caused by Streptococcus mutans (Kunze et al. 2010). Streptococcus
mutans forms biofilms that are sensitive to carolacton. Carolacton shows promising
results as an additive in dental filling material. The biofilm inhibition of carolacton
is comparable with that of triclosan and chlorhexidine. Carolacton also shows antifungal activity against Aspergillus niger, Pythium debaryanum and Sclerotina
sclerotiorum.
12.4.5.6 Inhibitors of Lipoprotein Processing
Lipoprotein signal peptidase A (LspA) is a type II signal peptidase involved in the
processing of lipoproteins, essential components for the survival of gram-negative
bacteria and to a certain extent for gram-positive bacteria. Lipoproteins are
12 Antimicrobials from Microbes
12.4.5.4 Inhibitors of Respiration
Three metabolites of the isoprenoid quinoline alkaloid group, namely, aurachin A
(Fig. 12.8d), B and C are produced by Stigmatella aurantiaca and members of
Rhodococcus species. Aurachins D and E are also isolated as minor products. All
aurachins share the quinoline nucleus substituted with a sesquiterpene. Aurachins
show a narrow spectrum of activity directed toward gram-positive bacteria and have
no effect on gram-negative bacteria. Aurachins also exhibit antiplasmodial activity
by inhibiting Plasmodium falsiparum in vitro. They show weak antifungal activity
against fungi like Debaryomyces hansenii and Saccharomyces cerevisiae. They
share structural similarities with the respiratory chain inhibitor 2-heptyl-4hydroxyquinoline-N-oxide (HQNO) and is able to prevent NADPH oxidation at
very low concentrations compared to HQNO.
Thuggacins are a group of macrolides containing a thiazol group produced by
Sorangium cellulosum strain So ce895. Four thuggacins are identified and named as
thuggacin A, B, C and methyl thuggacin A. In addition to the thiazole ring, thuggacins contain a diene moiety, an α, β unsaturated lactone with an n-hexyl side chain
attached at C-2 and an additional side chain at C-16 containing three hydroxyl and
a diene function. More thuggacins were isolated later from Chondromyces crocatus
strain Cm c5. Thuggacins exhibit antibacterial activity against gram-positive bacteria, including Micrococcus luteus. They also show activity against mycobacteria
like M. luteus, M. phlei, M. chitae and M. tuberculosis. Thuggacins bring about their
antibiotic effects by inhibiting the terminal stages of respiration thereby cutting
down the energy supply to the target cells (Steinmetz et al. 2007).
12.4.5.5 Inhibitors of Biofilm Formation
Biofilms offer increased resistance to antibiotics compared to free-living bacteria
because of the impermeable barrier created by biofilms to antibiotic penetration.
The search of antimicrobials that can disrupt biofilm structures is active. Carolacton
(Fig. 12.8e) is a macrolide antibiotic isolated from Sporangium cellulosum strain So
ce960 that show biofilm disruptive activity. The structure contains a 12-membered
lactone ring with two secondary hydroxyl groups at C-17 and C-18 and a terminal
carboxyl group on the side chain. Carolacton shows inhibitory activity against the
gram-negative bacterial strain E. coli tolC along with a disruptive action on bacterial biofilms. It showed promising activity against the formation of dental caries and
endocarditis caused by Streptococcus mutans (Kunze et al. 2010). Streptococcus
mutans forms biofilms that are sensitive to carolacton. Carolacton shows promising
results as an additive in dental filling material. The biofilm inhibition of carolacton
is comparable with that of triclosan and chlorhexidine. Carolacton also shows antifungal activity against Aspergillus niger, Pythium debaryanum and Sclerotina
sclerotiorum.
12.4.5.6 Inhibitors of Lipoprotein Processing
Lipoprotein signal peptidase A (LspA) is a type II signal peptidase involved in the
processing of lipoproteins, essential components for the survival of gram-negative
bacteria and to a certain extent for gram-positive bacteria. Lipoproteins are
12 Antimicrobials from Microbes