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regulator (AgrA) via phosphorylation relay. In turn, the activated AgrA upregulates
the expression of RNAIII and agr genes. In addition to that, AgrA regulated RNA
III also regulates the transcription of δ-toxin and various factors involved in virulence (Mayville et al. 1999).
(iii) Fsr quorum sensing system
In E. faecalis, Fsr quorum sensing system is related to pathogenicity of bacteria
due to its involvement in transcriptional regulation of gelatinase, an extracellular
metalloprotease and SprE proteases which are involved in the regulation of protein
expression and biofilm formation (Shankar et al. 2012; Kumar et al. 2019).
Gelatinase, in turn, cleaves the Ace, a microbial surface component recognizing
adhesive matrix molecule (MSCRAMM) of E. faecalis. Ace plays an essential role
in host cell adherence and virulence. The disruption of GelE and Fsr system significantly increases the adherence of E. faecalis on the cell surface of the host (Sifri
et al. 2002; Pinkston et al. 2011)
8.3.2 Self Signaling Pathway in Rap, NprR, PrgX,
and PlcR Family
In RNPP (Rap, NprR, PrgX, and PlcR) pathway, autoinducing peptides are ribosomally synthesized. The autoinducing peptides are modified post translationally
and secreted via SecA-dependent system. The main difference between a two component system and RNPP system is that after attaining a certain threshold concentration, these autoinducing peptides are carried inside the cells by proton dependent
oligopeptide transporters (POT); whereas, in two component system, autoinducing
peptides (AIPs) activate the sensor kinase. The phosphate regulator, Phr-AIPs were
first described in this class. The activated Phr-AIPs deactivates the Rap-phosphates
and plays a key role in sporulation and competence (McQuade et al. 2001).
(i) Phr-Rap system
Phr pro-autoinducing peptides are ribosomally synthesized carrying the signal
on N terminal for secretion. These pro-autoinducing peptides are cleaved by secreted
proteases to form a mature signal peptide. The mature Phr signal peptide is returned
back into the cell via oligopeptide permease (Opp), an ATP binding cassette (ABC)
transporter (Gardan et al. 2009). Phr regulate the gene expression by inhibiting the
regulator aspartate phosphatases (Raps). Raps are part of a complex variation of the
two component regulatory system i.e. phosphorelay system and regulate the transcription of several genes such as protease secretion in Bacillus subtilis (Koetje
et al. 2003). The rap and phr genes are co-transcribed. The proteins of Rap family
dephosphorylate the Spo0F, P (0F, P) to control sporulation of B. subtilis. In addition, the Rap proteins also inhibit the activity of ComA, a response regulator
involved in competence development and/or of DegU response regulator for the
production of secreted proteases. Kin proteins belong to the histidine sensor kinase
8 Intrusion of Bacterial Quorum-Sensing for Antimicrobial Resistance Mitigation…
regulator (AgrA) via phosphorylation relay. In turn, the activated AgrA upregulates
the expression of RNAIII and agr genes. In addition to that, AgrA regulated RNA
III also regulates the transcription of δ-toxin and various factors involved in virulence (Mayville et al. 1999).
(iii) Fsr quorum sensing system
In E. faecalis, Fsr quorum sensing system is related to pathogenicity of bacteria
due to its involvement in transcriptional regulation of gelatinase, an extracellular
metalloprotease and SprE proteases which are involved in the regulation of protein
expression and biofilm formation (Shankar et al. 2012; Kumar et al. 2019).
Gelatinase, in turn, cleaves the Ace, a microbial surface component recognizing
adhesive matrix molecule (MSCRAMM) of E. faecalis. Ace plays an essential role
in host cell adherence and virulence. The disruption of GelE and Fsr system significantly increases the adherence of E. faecalis on the cell surface of the host (Sifri
et al. 2002; Pinkston et al. 2011)
8.3.2 Self Signaling Pathway in Rap, NprR, PrgX,
and PlcR Family
In RNPP (Rap, NprR, PrgX, and PlcR) pathway, autoinducing peptides are ribosomally synthesized. The autoinducing peptides are modified post translationally
and secreted via SecA-dependent system. The main difference between a two component system and RNPP system is that after attaining a certain threshold concentration, these autoinducing peptides are carried inside the cells by proton dependent
oligopeptide transporters (POT); whereas, in two component system, autoinducing
peptides (AIPs) activate the sensor kinase. The phosphate regulator, Phr-AIPs were
first described in this class. The activated Phr-AIPs deactivates the Rap-phosphates
and plays a key role in sporulation and competence (McQuade et al. 2001).
(i) Phr-Rap system
Phr pro-autoinducing peptides are ribosomally synthesized carrying the signal
on N terminal for secretion. These pro-autoinducing peptides are cleaved by secreted
proteases to form a mature signal peptide. The mature Phr signal peptide is returned
back into the cell via oligopeptide permease (Opp), an ATP binding cassette (ABC)
transporter (Gardan et al. 2009). Phr regulate the gene expression by inhibiting the
regulator aspartate phosphatases (Raps). Raps are part of a complex variation of the
two component regulatory system i.e. phosphorelay system and regulate the transcription of several genes such as protease secretion in Bacillus subtilis (Koetje
et al. 2003). The rap and phr genes are co-transcribed. The proteins of Rap family
dephosphorylate the Spo0F, P (0F, P) to control sporulation of B. subtilis. In addition, the Rap proteins also inhibit the activity of ComA, a response regulator
involved in competence development and/or of DegU response regulator for the
production of secreted proteases. Kin proteins belong to the histidine sensor kinase
8 Intrusion of Bacterial Quorum-Sensing for Antimicrobial Resistance Mitigation…