194
expressions. The enhanced expression of RNAIII positively regulates the virulence
factors of bacteria. A substantial number of AgrC inhibitors have been identified as
the antagonist. Benzbromarone, an AIP based receptor antagonist is being used for
the treatment of infections caused by S. aureus strains (Gordon et al. 2013; Cech
and Horswill 2013). Another quorum quencher, savirin was identified by screening
the combinatorial library. Savirin inhibits the expression of RNAIII consequently,
the production of phenol soluble modulins (PSM) is inhibited. Phenol soluble modulins (PSMs) are staphylococcal toxins. In vivo experiments on mice also show that
savarin attenuate methicillin resistant Staphylococcus aureus, involved in skin and
soft tissue infections. Another strategy to inhibit quorum sensing is to prevent the
production of auto inducing peptides. SpsB is required for the processing of autoinducing peptide signal molecules. SpsB is a Type I signal peptidase. Inhibitors of
SpsB have the ability to quench the agr quorum sensing system of Staphylococcus
strains (Cech and Horswill 2013). In 2007, a study showed that some secondary
fungal metabolites are also capable to inhibit the bacterial quorum signaling.
Ambuic acid (KAP-21A), isolated from the fungal butanol extract was identified to
inhibit the gelatinase production without affecting the growth of Enterococcus faecalis. The production of gelatinase is mediated by FsrB, homologous to AgrB quorum sensing system. In addition, ambuic acid also significantly inhibits the
quormones, the quorum sensing hormones produced by S. aureus, L. innocua and
other Gram positive bacteria (Nakayama et al. 2009). Two cyclic dipeptides, cyclo
(L-Phe-L-Pro) and cyclo (L-Tyr-L-Pro) secreted by Lactobacillus reuteri RC-14, a
human vaginal isolate were identified as staphylococcal agr quorum quencher (Li
et al. 2011). Other natural compounds 1,3,6-trihydroxy-8-methyl-xanthone (norlichexanthone) and 1,3,5,6-trihydroxy-8-methyl-xanthone also act as anti virulent
drugs against S. aureus (Nielsen et al. 2010). Still, the traditional approaches are
being used to treat bacterial infections. The antibiotics having bacteriostatic or bactericidal activities are being used for this purpose but their unrestrictive use has led
to the antibiotic resistance in bacteria. Recent studies suggest the forthcoming
potential of quorum sensing inhibitors as anti pathogenic drugs to control the
expression of virulence factors of antibiotic resistant bacteria.
8.7 Clinical Trials of Quorum Sensing Inhibitors
Only, the previously commercialized and approved antimicrobials are being used in
the clinical trials for their potential to inhibit quorum sensing system. Their antimicrobial activities and cytotoxicity were tested but their effects on quorum sensing
were still untouched. In the earlier studies, the azithromycin was used for the treatment of bacterial infections. This antibiotic improved the patient’s condition but did
not decrease bacterial load (Saiman et al. 2003). In 2001, studies showed that at
non-bactericidal concentrations, azithromycin disrupts the quorum sensing signaling in antibiotic resistant P. aeruginosa in ventilator associated pneumonia (Tateda
et al. 2001; van Delden et al. 2012). Garlic, known as a prophylactic agent due to its
S. Kumar et al.
expressions. The enhanced expression of RNAIII positively regulates the virulence
factors of bacteria. A substantial number of AgrC inhibitors have been identified as
the antagonist. Benzbromarone, an AIP based receptor antagonist is being used for
the treatment of infections caused by S. aureus strains (Gordon et al. 2013; Cech
and Horswill 2013). Another quorum quencher, savirin was identified by screening
the combinatorial library. Savirin inhibits the expression of RNAIII consequently,
the production of phenol soluble modulins (PSM) is inhibited. Phenol soluble modulins (PSMs) are staphylococcal toxins. In vivo experiments on mice also show that
savarin attenuate methicillin resistant Staphylococcus aureus, involved in skin and
soft tissue infections. Another strategy to inhibit quorum sensing is to prevent the
production of auto inducing peptides. SpsB is required for the processing of autoinducing peptide signal molecules. SpsB is a Type I signal peptidase. Inhibitors of
SpsB have the ability to quench the agr quorum sensing system of Staphylococcus
strains (Cech and Horswill 2013). In 2007, a study showed that some secondary
fungal metabolites are also capable to inhibit the bacterial quorum signaling.
Ambuic acid (KAP-21A), isolated from the fungal butanol extract was identified to
inhibit the gelatinase production without affecting the growth of Enterococcus faecalis. The production of gelatinase is mediated by FsrB, homologous to AgrB quorum sensing system. In addition, ambuic acid also significantly inhibits the
quormones, the quorum sensing hormones produced by S. aureus, L. innocua and
other Gram positive bacteria (Nakayama et al. 2009). Two cyclic dipeptides, cyclo
(L-Phe-L-Pro) and cyclo (L-Tyr-L-Pro) secreted by Lactobacillus reuteri RC-14, a
human vaginal isolate were identified as staphylococcal agr quorum quencher (Li
et al. 2011). Other natural compounds 1,3,6-trihydroxy-8-methyl-xanthone (norlichexanthone) and 1,3,5,6-trihydroxy-8-methyl-xanthone also act as anti virulent
drugs against S. aureus (Nielsen et al. 2010). Still, the traditional approaches are
being used to treat bacterial infections. The antibiotics having bacteriostatic or bactericidal activities are being used for this purpose but their unrestrictive use has led
to the antibiotic resistance in bacteria. Recent studies suggest the forthcoming
potential of quorum sensing inhibitors as anti pathogenic drugs to control the
expression of virulence factors of antibiotic resistant bacteria.
8.7 Clinical Trials of Quorum Sensing Inhibitors
Only, the previously commercialized and approved antimicrobials are being used in
the clinical trials for their potential to inhibit quorum sensing system. Their antimicrobial activities and cytotoxicity were tested but their effects on quorum sensing
were still untouched. In the earlier studies, the azithromycin was used for the treatment of bacterial infections. This antibiotic improved the patient’s condition but did
not decrease bacterial load (Saiman et al. 2003). In 2001, studies showed that at
non-bactericidal concentrations, azithromycin disrupts the quorum sensing signaling in antibiotic resistant P. aeruginosa in ventilator associated pneumonia (Tateda
et al. 2001; van Delden et al. 2012). Garlic, known as a prophylactic agent due to its
S. Kumar et al.