Part B | 15.3
434 Part B Tools and Methods in Marine Biotechnology
have anti-QS potential. Epigallocatechin gallate (salt
of gallic acid) and ellagic acid inhibited LasR and
LuxR-based QS at the concentrations 1530 M. Gallic, but not ellagic, acid inhibited QS of C. violaceum CVO17 at 64:7 M. Ellagic acid derivatives
from Terminalia chebula Retz. fruit downregulate the
expression of lasI/R and rhlI/R QS genes and attenuate P. aeruginosa PAO1 virulence. They also enhance the sensitivity of its biofilm towards the tobramycin antibiotic. Biomolecules like Hymenialdisine, demethoxyencecalin, microcolins A and B, and
kojic acid have been shown to inhibit LuxR-based
reporters (E. coli pSB401) induced by 3OC 6 HSL at
concentrations ranging from 0:2 M to 36 M. The
ability to prevent microfouling by kojic acid at 330 M
and 1 mM was observed by a decrease in the cell
densities of bacteria and diatoms. Inhibitory concentration of hymenialdisine, demethoxyencecalin, kojic acid, and microcolins A and B were comparable
with ones of natural furanones, ellagic acid, malyngolide and manoalide. Other antibiotics such as –
azithromycin, ceftazidime, and ciprofloxacin inhibited
the QS of LuxR-based reporters based on the QS
circuit of Vibrio fischeri at sub-lethal concentrations
ranging between 0:111 M [15.3, 9]. Even fruit and
spices consumed as food in our day to day life have
molecules with the ability to inhibit the QS of bacterial
pathogens [15.18–21].
Marine Derivatives as QSIs
Extracts of Great Barrier Reef marine invertebrates
and cyanobacteria act as QSIs against bacteria. Biochemical defenses against fouling are widely deployed
by algae. Metabolites that affect microbial communities have been demonstrated in the red algal family
Bonnesmaisoniae for Delisea pulchra, Asparagopsis
armata and Bonnesmaisonoa hamifera. The most wellinvestigated example of this defensive strategy is that of
the red alga, D. pulchra, which produces halogenated
furanones at the surface of the thallus. A high concentration of metabolites at the surface strongly inhibits QS
by targeting AHL-dependent signals, and thus the settlement of various fouling propagules, and deters the
settlement and growth of both micro and macrofouling agents. Natural chemical defenses are not restricted
to the red algal models, as the secondary metabolites
from Dictyota menstraulis and phlorotannins from Fucus evanescens also have AF activity. Ursine triterpenes
from Diospyros dendo also interfere with QS. Oxidized
halogen (HOBr) from Laminaria digitata, a brown alga,
reacts specifically with 3-oxo-acyl HSLs. Marine bacteria produce QSIs that interfere with the formation
of biofilms. For example, the bacterium Aeromonas
veronii inhibits QS through competition for AHL production. TAGE (trans-bromo ageliferin analog) and
CAGE (cis-bromo ageliferin analog) are two derivatives
of the marine natural product bromo ageliferin. Both
compounds have been shown to be effective inhibitors
of P. aeruginosa, Staphylococcus aureus, Acinetobacter baumannii, and Bordetella bronchiseptica biofilm
formation. There are only a few studies on marine
microbes and their metabolites with respect to their
antibiofilm activities. This is because the majority (<
95%) of phylogenetic clades of marine bacteria cannot
be cultivated in laboratories. AF metabolites from noncultivable marine microbes can be obtained through a
metagenomic approach [15.22].
Biomolecules produced by bacteria associated with
sponges have been a very good source of QSIs. Extracts of bacteria such as Bacillus horikoshi, B. pumilus,
and Vibrio natrigens, associated with the coral Acropora digitifera, have been found to display efficient
activities against biofilm-forming Streptococcus pyogenes. Among these bacteria, B. horikoshi proved more
efficient at a concentration of 50 g mL
1 , in contrast to the other two strains, which were effective at
100 g mL
1 . In a subsequent study, Bacillus indicus,
B. pumilus, and Bacillus sp. SS4 from Palk Bay (Bay
of Bengal) were shown to cause significant inhibition
of QS-based activities in Gram-negative bacteria such
as P. aeruginosa PAO1, Serratia marcescens, and Vibrio species. Marine bacterium B. pumilus S6-15 was
found to have a wider application in its ability to
inhibit biofilm formation in both Gram-positive and
Gram-negative bacteria. The active principles were the
enzyme acylase and other secondary metabolites like
carboxylic acid derivatives (4-phenylbutanoic acid).
These QSIs were also found to inhibit the intestinal
colonization of S. aureus in nematode Caenorhabditis
elegans and its subsequent killing [15.23–30].
Bacteria in a biofilm can also affect the growth of
other bacteria in the same biofilm. The marine bacterium Alteromonas sp. produces antibiotic 2-n-phenyl4-quinolinol, which alters the composition of the bacterial community developed on particles. To date, only
two classes of marine sponge metabolites house nonbactericidal biofilm modulators, viz. terpenoids and
pyrrole-imidazoles. Terpenes are structurally diverse
molecules, and this diversity is contributed by their isoprene subunits. The biological activities of terpenes are
also diverse, ranging from AF effects to antiproliferative cancer therapeutics [15.31].
434 Part B Tools and Methods in Marine Biotechnology
have anti-QS potential. Epigallocatechin gallate (salt
of gallic acid) and ellagic acid inhibited LasR and
LuxR-based QS at the concentrations 1530 M. Gallic, but not ellagic, acid inhibited QS of C. violaceum CVO17 at 64:7 M. Ellagic acid derivatives
from Terminalia chebula Retz. fruit downregulate the
expression of lasI/R and rhlI/R QS genes and attenuate P. aeruginosa PAO1 virulence. They also enhance the sensitivity of its biofilm towards the tobramycin antibiotic. Biomolecules like Hymenialdisine, demethoxyencecalin, microcolins A and B, and
kojic acid have been shown to inhibit LuxR-based
reporters (E. coli pSB401) induced by 3OC 6 HSL at
concentrations ranging from 0:2 M to 36 M. The
ability to prevent microfouling by kojic acid at 330 M
and 1 mM was observed by a decrease in the cell
densities of bacteria and diatoms. Inhibitory concentration of hymenialdisine, demethoxyencecalin, kojic acid, and microcolins A and B were comparable
with ones of natural furanones, ellagic acid, malyngolide and manoalide. Other antibiotics such as –
azithromycin, ceftazidime, and ciprofloxacin inhibited
the QS of LuxR-based reporters based on the QS
circuit of Vibrio fischeri at sub-lethal concentrations
ranging between 0:111 M [15.3, 9]. Even fruit and
spices consumed as food in our day to day life have
molecules with the ability to inhibit the QS of bacterial
pathogens [15.18–21].
Marine Derivatives as QSIs
Extracts of Great Barrier Reef marine invertebrates
and cyanobacteria act as QSIs against bacteria. Biochemical defenses against fouling are widely deployed
by algae. Metabolites that affect microbial communities have been demonstrated in the red algal family
Bonnesmaisoniae for Delisea pulchra, Asparagopsis
armata and Bonnesmaisonoa hamifera. The most wellinvestigated example of this defensive strategy is that of
the red alga, D. pulchra, which produces halogenated
furanones at the surface of the thallus. A high concentration of metabolites at the surface strongly inhibits QS
by targeting AHL-dependent signals, and thus the settlement of various fouling propagules, and deters the
settlement and growth of both micro and macrofouling agents. Natural chemical defenses are not restricted
to the red algal models, as the secondary metabolites
from Dictyota menstraulis and phlorotannins from Fucus evanescens also have AF activity. Ursine triterpenes
from Diospyros dendo also interfere with QS. Oxidized
halogen (HOBr) from Laminaria digitata, a brown alga,
reacts specifically with 3-oxo-acyl HSLs. Marine bacteria produce QSIs that interfere with the formation
of biofilms. For example, the bacterium Aeromonas
veronii inhibits QS through competition for AHL production. TAGE (trans-bromo ageliferin analog) and
CAGE (cis-bromo ageliferin analog) are two derivatives
of the marine natural product bromo ageliferin. Both
compounds have been shown to be effective inhibitors
of P. aeruginosa, Staphylococcus aureus, Acinetobacter baumannii, and Bordetella bronchiseptica biofilm
formation. There are only a few studies on marine
microbes and their metabolites with respect to their
antibiofilm activities. This is because the majority (<
95%) of phylogenetic clades of marine bacteria cannot
be cultivated in laboratories. AF metabolites from noncultivable marine microbes can be obtained through a
metagenomic approach [15.22].
Biomolecules produced by bacteria associated with
sponges have been a very good source of QSIs. Extracts of bacteria such as Bacillus horikoshi, B. pumilus,
and Vibrio natrigens, associated with the coral Acropora digitifera, have been found to display efficient
activities against biofilm-forming Streptococcus pyogenes. Among these bacteria, B. horikoshi proved more
efficient at a concentration of 50 g mL
1 , in contrast to the other two strains, which were effective at
100 g mL
1 . In a subsequent study, Bacillus indicus,
B. pumilus, and Bacillus sp. SS4 from Palk Bay (Bay
of Bengal) were shown to cause significant inhibition
of QS-based activities in Gram-negative bacteria such
as P. aeruginosa PAO1, Serratia marcescens, and Vibrio species. Marine bacterium B. pumilus S6-15 was
found to have a wider application in its ability to
inhibit biofilm formation in both Gram-positive and
Gram-negative bacteria. The active principles were the
enzyme acylase and other secondary metabolites like
carboxylic acid derivatives (4-phenylbutanoic acid).
These QSIs were also found to inhibit the intestinal
colonization of S. aureus in nematode Caenorhabditis
elegans and its subsequent killing [15.23–30].
Bacteria in a biofilm can also affect the growth of
other bacteria in the same biofilm. The marine bacterium Alteromonas sp. produces antibiotic 2-n-phenyl4-quinolinol, which alters the composition of the bacterial community developed on particles. To date, only
two classes of marine sponge metabolites house nonbactericidal biofilm modulators, viz. terpenoids and
pyrrole-imidazoles. Terpenes are structurally diverse
molecules, and this diversity is contributed by their isoprene subunits. The biological activities of terpenes are
also diverse, ranging from AF effects to antiproliferative cancer therapeutics [15.31].