179
Gram positive bacteria. When the concentration of autoinducer is high, they bind to
the two component membrane bound histidine kinase receptors. The binding of
autoinducer activates the kinase activity of the receptor that auto phosphorylates at
a conserved histidine residue and transfers this phosphate to a cognate response
regulator to activate the quorum sensing genes (Figure 8.1a). In few instances, autoinducers are transported back into the cytoplasm which then interacts with the transcription factors to regulate quorum sensing genes (Figure 8.1b). Gram negative
bacteria use small molecules such as acyl-homoserine lactones (acyl HSL) for communication. S- adenosylmethionine (SAM) is the substrate for the production of
AHLs in the cell. When the concentration of autoinducer is high in the surrounding
environment, they bind to transcription factors present in the cytoplasm and regulate
the transcription of genes of quorum sensing regulon (Figure 8.1c). In a few cases,
AIs are also sensed by histidine kinase receptors of a bacterial two component system that have analogous functions to Gram positive quorum sensing system as
shown in Figure 8.1d (Swift et al. 2001; Wei et al. 2011).
Quorum sensing plays an important role in the pathogenicity of bacteria such as
the synthesis of elastase, lectin, pyocyanin, and exotoxin A in Pseudomonas aeruginosa is regulated by quorum sensing system. The quorum sensing also regulates
the production and secretion of enterotoxins, hemolysins, cytotoxins, lipases, protein A, fibronectin protein, etc. in Staphylococcus aureus (Jiang et al. 2019). These
virulence factors evade the immune system of the host to obtain nutrition. Many
quorum sensing inhibitors have been identified as agents that inhibit the activity of
virulence factors in pathogenic bacteria. The clinical trials are under investigation to
explore their application in pharmaceuticals and therapeutics such as for the treatment of antibiotic resistant bacteria, as an anti biofilm forming agent in new generation medical devices, etc. The goal of this chapter is to introduce the types of quorum
sensing and the potential of quorum sensing inhibitors as a therapeutic agent for the
prevention of infections due to resistant pathogenic bacteria.
8.2 Quorum Sensing System in Gram Negative Bacteria
8.2.1 N-Acylhomoserine Lactone Signaling
N-acylhomoserine lactones (acyl-HSL) are the most studied family of QS signaling
molecules. Generally, Gram negative bacteria such as Aeromonas, Burkholderia,
Brucella, Pseudomonas, and Serratia use the acyl-HSL molecules for signaling
(Swift et al. 2001; Williams 2002). The basic structure of acyl-HSL is similar, consisting of a homoserine lactone ring and acyl chain that vary in length (from 4 to 18
carbons), oxidation states and saturation levels (Fig. 8.2). This variation in the acyl
chain enables bacteria to recognize and differentiate between their own acyl-HSL
and others (Kumari et al. 2006). These signal molecules are synthesized by
8 Intrusion of Bacterial Quorum-Sensing for Antimicrobial Resistance Mitigation…
Gram positive bacteria. When the concentration of autoinducer is high, they bind to
the two component membrane bound histidine kinase receptors. The binding of
autoinducer activates the kinase activity of the receptor that auto phosphorylates at
a conserved histidine residue and transfers this phosphate to a cognate response
regulator to activate the quorum sensing genes (Figure 8.1a). In few instances, autoinducers are transported back into the cytoplasm which then interacts with the transcription factors to regulate quorum sensing genes (Figure 8.1b). Gram negative
bacteria use small molecules such as acyl-homoserine lactones (acyl HSL) for communication. S- adenosylmethionine (SAM) is the substrate for the production of
AHLs in the cell. When the concentration of autoinducer is high in the surrounding
environment, they bind to transcription factors present in the cytoplasm and regulate
the transcription of genes of quorum sensing regulon (Figure 8.1c). In a few cases,
AIs are also sensed by histidine kinase receptors of a bacterial two component system that have analogous functions to Gram positive quorum sensing system as
shown in Figure 8.1d (Swift et al. 2001; Wei et al. 2011).
Quorum sensing plays an important role in the pathogenicity of bacteria such as
the synthesis of elastase, lectin, pyocyanin, and exotoxin A in Pseudomonas aeruginosa is regulated by quorum sensing system. The quorum sensing also regulates
the production and secretion of enterotoxins, hemolysins, cytotoxins, lipases, protein A, fibronectin protein, etc. in Staphylococcus aureus (Jiang et al. 2019). These
virulence factors evade the immune system of the host to obtain nutrition. Many
quorum sensing inhibitors have been identified as agents that inhibit the activity of
virulence factors in pathogenic bacteria. The clinical trials are under investigation to
explore their application in pharmaceuticals and therapeutics such as for the treatment of antibiotic resistant bacteria, as an anti biofilm forming agent in new generation medical devices, etc. The goal of this chapter is to introduce the types of quorum
sensing and the potential of quorum sensing inhibitors as a therapeutic agent for the
prevention of infections due to resistant pathogenic bacteria.
8.2 Quorum Sensing System in Gram Negative Bacteria
8.2.1 N-Acylhomoserine Lactone Signaling
N-acylhomoserine lactones (acyl-HSL) are the most studied family of QS signaling
molecules. Generally, Gram negative bacteria such as Aeromonas, Burkholderia,
Brucella, Pseudomonas, and Serratia use the acyl-HSL molecules for signaling
(Swift et al. 2001; Williams 2002). The basic structure of acyl-HSL is similar, consisting of a homoserine lactone ring and acyl chain that vary in length (from 4 to 18
carbons), oxidation states and saturation levels (Fig. 8.2). This variation in the acyl
chain enables bacteria to recognize and differentiate between their own acyl-HSL
and others (Kumari et al. 2006). These signal molecules are synthesized by
8 Intrusion of Bacterial Quorum-Sensing for Antimicrobial Resistance Mitigation…