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Synthetic Quorum Sensing Inhibitors (QSIs) Blocking Receptor Signaling or Signal Molecule Biosynthesis in Pseudomonas aeruginosa

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Quorum Sensing vs Quorum Quenching: A Battle with No End in Sight

Abstract

Pseudomonas aeruginosa masters quorum sensing (QS) communication to coordinately regulate pathogenicity-associated group behaviors including the production of virulence factors and biofilm formation, which facilitate the invasion into the hosts, counteract host immune system, as well as promote the resistance/tolerance toward conventional antibiotics. Three main QS systems are employed by the pathogen, denoted as las (Gambello and Iglewski 1991; Passador et al. 1993), rhl (Ochsner et al. 1994; Ochsner and Reiser 1995), and pqs (Pesci et al. 1999). All the networks are hierarchically interconnected: las controls the other two systems; pqs positively regulates the rhl signaling, whereas rhl in turn puts a negative feedback upon pqs (Wilder et al. 2011; McGrath et al. 2004). Regarding the central role of QS for the infectious process, the interruption of these pathways by blocking the receptors or inhibiting the signal synthesis via small molecules is an attractive therapeutic strategy to attenuate the bacterial pathogenicity, thereby overcoming intractable P. aeruginosa infections (Rasmussen and Givskov 2006).

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Abbreviations

ACP:

Acyl carrier protein

AHL:

N-acyl homoserine lactone

AMP:

Adenosine monophosphate

ATP:

Adenosine triphosphate

C4-HSL:

N-butanoyl-l-homoserine lactone

CoA:

Coenzyme A

HAQ:

4-hydroxy-2-alkylquinoline

HHQ:

2-heptyl-4-hydroxyquinoline

IC50 :

Inhibitor concentration to achieve a half-maximal degree of inhibition

MTA:

5-methylthioadenosine

NADH/ NAD+ :

Reduced/oxidized form of nicotinamide adenine dinucleotide

3-oxo-C12 -HSL:

N-(3-oxo-dodecanoyl)-l-homoserine lactone

PPi :

Pyrophosphate

PQS:

Pseudomonas quinolone signal

QS:

Quorum sensing

QSI:

Quorum sensing inhibitor

QZN:

Quinazolinone

RNAP:

RNA polymerase

SAM:

l-S-adenosylmethionine

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Authors and Affiliations

  1. Department Drug Design and Optimization, Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Campus C2.3, 66123, Saarbrücken, Germany

    Christine K. Maurer, Cenbin Lu, Martin Empting & Rolf W. Hartmann

  2. Pharmaceutical and Medicinal Chemistry at the Saarland University, Campus C2.3, 66123, Saarbrücken, Germany

    Rolf W. Hartmann

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  1. Christine K. Maurer
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  2. Cenbin Lu
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  3. Martin Empting
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  4. Rolf W. Hartmann
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Correspondence to Rolf W. Hartmann .

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  1. CSIR-Institute of Genomics and Integrative Biology, Microbial Biotechnology and Genomics, Delhi, India

    Vipin Chandra Kalia

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Maurer, C.K., Lu, C., Empting, M., Hartmann, R.W. (2015). Synthetic Quorum Sensing Inhibitors (QSIs) Blocking Receptor Signaling or Signal Molecule Biosynthesis in Pseudomonas aeruginosa . In: Kalia, V. (eds) Quorum Sensing vs Quorum Quenching: A Battle with No End in Sight. Springer, New Delhi. https://doi.org/10.1007/978-81-322-1982-8_24

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