189
(Tiaden and Hilbi 2012), fatty acids are used by Burkholderia spp., Xanthomonas
spp., Xylella spp. (Zhou et al. 2017), quinolones are used by Pseudomonas aeruginosa (Heeb et al. 2011) and epinephrine, nor-epinephrine, and AI-3 are used by
enterohemorrhagic bacteria (Kendall and Sperandio 2007). The furanosyl borate
diester, an auto inducing peptide (AI-2) is used by both Gram positive and Gram
negative bacteria (Chen et al. 2002). Vibrio harveyi, a free living bioluminescent
marine bacterium uses the furanosyl borate diester as a signaling molecule for bioluminescence (Skandamis and Nychas 2012). Some Gram negative bacteria integrate the different quorum sensing systems to act in a network such as P. aeruginosa
uses four quorum sensing systems namely, las, rhl, iqs, and pqs. These four systems
are interconnected with each other to regulate the pathogenicity of P. aeruginosa.
Quorum sensing systems namely, las, iqs, and pqs invoke the rhl expression that
enables the bacteria to survive in adverse conditions (Lee and Zhang 2015).
Quorum quenching is the disruption of the bacterial quorum sensing system.
Quorum quenching is a natural phenomenon used by bacteria to degrade quorum
sensing signaling molecules and was first described in Erwinia carotovora (Rémy
et al. 2018). Inhibitors of Quorum sensing are produced by bacteria in order to
inhibit the action of auto inducing peptides and quorum quenching enzymes resulting in the interference with quorum sensing mechanism. Inhibitors of Quorum sensing are listed in Table 8.1. The use of these inhibitors as therapeutic agents might be
a promising strategy to reduce bacterial pathogenicity. These strategies may be used
to enhance bacterial susceptibility to antibiotics and to decrease biofilm formation.
The communication between bacteria can be disrupted by several mechanisms such
as: (i) by the production of quorum sensing inhibitors which intervene with the
autoinducer production (Tang and Zhang 2014), (ii) Utilizing quorum quenching
antibodies (Park et al. 2007), and macromolecules like cyclodextrins to remove AIs
(Morohoshi et al. 2013), or (iii) by disintegrating AIs using hydrolyzing quorum
quenching enzymes (Fetzner 2015a). A wide number of small molecules and antagonist peptides have been discovered to inhibit or quench the quorum sensing molecules (Tang and Zhang 2014).
There are multiple methods to identify novel inhibitors and quenchers such as
computer aided drug screening, high throughput screening, random screening and
purification from crude extracts, etc. In addition to that many genetically modified
strains that express reporter genes, are being used as quorum sensing biosensors to
identify inhibitors. The inhibitors and quencher molecules can be either natural
products such as ajoene from garlic, polyphenols of tea and honey, eugenol from
clove and products from marine organisms or synthetic products such as azithromycin and 5-fluorouracil (5-FU) (Swatton et al. 2016; Delago et al. 2016). Besides the
small molecules, some quorum quenching enzymes have been identified to target
the AI-2 and AHLs molecules involved in quorum sensing. The main enzymes are
lactonases, acylases, and oxidoreductases that degrade the AI-2 and AHL signaling
molecules (Fetzner 2015b; Bzdrenga et al. 2017a). The quorum quenching enzymes
are classified into two groups: Class I enzymes are the AHL-lactonase, AHLacylase, and paraoxonase, which degrade the AHL molecules and, class II enzymes
are oxidoreductases, which reduce the carbonyl to hydroxyl. The disruption of
8 Intrusion of Bacterial Quorum-Sensing for Antimicrobial Resistance Mitigation…
(Tiaden and Hilbi 2012), fatty acids are used by Burkholderia spp., Xanthomonas
spp., Xylella spp. (Zhou et al. 2017), quinolones are used by Pseudomonas aeruginosa (Heeb et al. 2011) and epinephrine, nor-epinephrine, and AI-3 are used by
enterohemorrhagic bacteria (Kendall and Sperandio 2007). The furanosyl borate
diester, an auto inducing peptide (AI-2) is used by both Gram positive and Gram
negative bacteria (Chen et al. 2002). Vibrio harveyi, a free living bioluminescent
marine bacterium uses the furanosyl borate diester as a signaling molecule for bioluminescence (Skandamis and Nychas 2012). Some Gram negative bacteria integrate the different quorum sensing systems to act in a network such as P. aeruginosa
uses four quorum sensing systems namely, las, rhl, iqs, and pqs. These four systems
are interconnected with each other to regulate the pathogenicity of P. aeruginosa.
Quorum sensing systems namely, las, iqs, and pqs invoke the rhl expression that
enables the bacteria to survive in adverse conditions (Lee and Zhang 2015).
Quorum quenching is the disruption of the bacterial quorum sensing system.
Quorum quenching is a natural phenomenon used by bacteria to degrade quorum
sensing signaling molecules and was first described in Erwinia carotovora (Rémy
et al. 2018). Inhibitors of Quorum sensing are produced by bacteria in order to
inhibit the action of auto inducing peptides and quorum quenching enzymes resulting in the interference with quorum sensing mechanism. Inhibitors of Quorum sensing are listed in Table 8.1. The use of these inhibitors as therapeutic agents might be
a promising strategy to reduce bacterial pathogenicity. These strategies may be used
to enhance bacterial susceptibility to antibiotics and to decrease biofilm formation.
The communication between bacteria can be disrupted by several mechanisms such
as: (i) by the production of quorum sensing inhibitors which intervene with the
autoinducer production (Tang and Zhang 2014), (ii) Utilizing quorum quenching
antibodies (Park et al. 2007), and macromolecules like cyclodextrins to remove AIs
(Morohoshi et al. 2013), or (iii) by disintegrating AIs using hydrolyzing quorum
quenching enzymes (Fetzner 2015a). A wide number of small molecules and antagonist peptides have been discovered to inhibit or quench the quorum sensing molecules (Tang and Zhang 2014).
There are multiple methods to identify novel inhibitors and quenchers such as
computer aided drug screening, high throughput screening, random screening and
purification from crude extracts, etc. In addition to that many genetically modified
strains that express reporter genes, are being used as quorum sensing biosensors to
identify inhibitors. The inhibitors and quencher molecules can be either natural
products such as ajoene from garlic, polyphenols of tea and honey, eugenol from
clove and products from marine organisms or synthetic products such as azithromycin and 5-fluorouracil (5-FU) (Swatton et al. 2016; Delago et al. 2016). Besides the
small molecules, some quorum quenching enzymes have been identified to target
the AI-2 and AHLs molecules involved in quorum sensing. The main enzymes are
lactonases, acylases, and oxidoreductases that degrade the AI-2 and AHL signaling
molecules (Fetzner 2015b; Bzdrenga et al. 2017a). The quorum quenching enzymes
are classified into two groups: Class I enzymes are the AHL-lactonase, AHLacylase, and paraoxonase, which degrade the AHL molecules and, class II enzymes
are oxidoreductases, which reduce the carbonyl to hydroxyl. The disruption of
8 Intrusion of Bacterial Quorum-Sensing for Antimicrobial Resistance Mitigation…