184
transduction. In certain cases, immature autoinducing peptides are secreted by the
bacteria. These secreted precursor autoinducing peptides are processed by the extracellular proteases into mature autoinducing peptides. After maturation, these peptides return back to the cells to regulate the activity of transcription factors (Kievit
and Iglewski 2000). In Gram positive bacteria, there are two major pathways of
quorum sensing.
8.3.1 Two Component Pathway
In the two component system pathway, autoinducing peptides are ribosomally synthesized and secreted via peptide ABC transporters. The secreted autoinducing peptides are modified post translationally and processed by proteases to form mature
autoinducing peptides. After attaining a certain threshold concentration, they interact with the histidine kinases, specific receptors on the cell surface. This interaction
activates the kinase by phosphorylating it at conserved histidine residue that subsequently activates the cognate response regulator by transferring this phosphate to
conserved aspartate residue to regulate the secretion of autoinducing peptides and
transcription of target genes (Bhatt 2018).
(i) Competence system
S. pneumoniae and B. subtilis employ a competence system (Com) for the uptake
of exogenous DNA. B. subtilis also utilize this system to form homodimers of regulatory receptor to bind the inverted repeats of DNA (Bhatt 2018). The precursor
autoinducing signal peptide is initially synthesized as 41 amino acid peptide known
as ComC which is processed to form 17 amino acids mature autoinducing peptide
called CSP (competence stimulating peptide). The ComAB ABC transporter
secretes matured CSP. At high cell density, CSP reaches the critical threshold and
detected via dedicated ComD histidine sensor kinase protein of the two component
system. The activated histidine kinase undergoes autophosphorylation and the phosphoryl group is transferred to the response regulator, ComE (Pestova et al. 1996).
Subsequently, phosphorylated ComE activates the transcription of comX gene, an
alternative σ factor that mediates the transcription of structural genes involved in
competence development (Lee and Morrison 1999).
(ii) Accessory Gene Regulator system
S. aureus pathogenicity is regulated by the peptide quorum sensing mechanism.
The cell density dependent pathogenicity is regulated by RNAIII, an RNA molecule. AgrBDCA (accessory gene regulator) operon encodes several proteins,
namely, AgrA, AgrB, AgrC and AgrD that regulate the RNAIII expression. The
AgrD encodes the 46 amino acid precursor signal peptide that is proteolytically
cleaved by AgrB resulting in thiolactone intermediate and then secreted. The final
mature and active form is obtained upon subsequent cleavage (Novick et al. 1995).
After attaining the critical threshold concentration, autoinducing peptide activates
the sensor histidine kinase (AgrC) that further activate the intracellular response
S. Kumar et al.
transduction. In certain cases, immature autoinducing peptides are secreted by the
bacteria. These secreted precursor autoinducing peptides are processed by the extracellular proteases into mature autoinducing peptides. After maturation, these peptides return back to the cells to regulate the activity of transcription factors (Kievit
and Iglewski 2000). In Gram positive bacteria, there are two major pathways of
quorum sensing.
8.3.1 Two Component Pathway
In the two component system pathway, autoinducing peptides are ribosomally synthesized and secreted via peptide ABC transporters. The secreted autoinducing peptides are modified post translationally and processed by proteases to form mature
autoinducing peptides. After attaining a certain threshold concentration, they interact with the histidine kinases, specific receptors on the cell surface. This interaction
activates the kinase by phosphorylating it at conserved histidine residue that subsequently activates the cognate response regulator by transferring this phosphate to
conserved aspartate residue to regulate the secretion of autoinducing peptides and
transcription of target genes (Bhatt 2018).
(i) Competence system
S. pneumoniae and B. subtilis employ a competence system (Com) for the uptake
of exogenous DNA. B. subtilis also utilize this system to form homodimers of regulatory receptor to bind the inverted repeats of DNA (Bhatt 2018). The precursor
autoinducing signal peptide is initially synthesized as 41 amino acid peptide known
as ComC which is processed to form 17 amino acids mature autoinducing peptide
called CSP (competence stimulating peptide). The ComAB ABC transporter
secretes matured CSP. At high cell density, CSP reaches the critical threshold and
detected via dedicated ComD histidine sensor kinase protein of the two component
system. The activated histidine kinase undergoes autophosphorylation and the phosphoryl group is transferred to the response regulator, ComE (Pestova et al. 1996).
Subsequently, phosphorylated ComE activates the transcription of comX gene, an
alternative σ factor that mediates the transcription of structural genes involved in
competence development (Lee and Morrison 1999).
(ii) Accessory Gene Regulator system
S. aureus pathogenicity is regulated by the peptide quorum sensing mechanism.
The cell density dependent pathogenicity is regulated by RNAIII, an RNA molecule. AgrBDCA (accessory gene regulator) operon encodes several proteins,
namely, AgrA, AgrB, AgrC and AgrD that regulate the RNAIII expression. The
AgrD encodes the 46 amino acid precursor signal peptide that is proteolytically
cleaved by AgrB resulting in thiolactone intermediate and then secreted. The final
mature and active form is obtained upon subsequent cleavage (Novick et al. 1995).
After attaining the critical threshold concentration, autoinducing peptide activates
the sensor histidine kinase (AgrC) that further activate the intracellular response
S. Kumar et al.
