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Chapter 24 : Quorum Quenching: Impact and Mechanisms
Category: Microbial Genetics and Molecular Biology; Bacterial Pathogenesis
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This chapter focuses on the impact and molecular mechanisms of quorum quenching, with emphasis on quorum-quenching enzymes and other signal disruption mechanisms. There are five key processes in quorum-sensing circuit, (i) signal generation, (ii) signal transportation, (iii) signal accumulation, (iv) signal recognition, and (v) signal autoinduction. The authors have confirmed recently that replacement of His104 with alanine in AiiA240B1 almost completely abolishes the enzyme activity. By sequence alignment, it was found that all the residues implicated in metal coordination are conserved in the reported acyl-homoserine lactone (AHL)-lactonases. In contrast to the three groups of enzymes, i.e., AHL-lactonase, PON enzymes, and AHL-acylase, which degrade AHL signals by breaking the bond in either the lactone ring or in the junction connecting fatty acid moiety and homoserine lactone component, AHL-oxidoreductase modifies the 3-oxo group of the AHL signals with the corresponding substitution to generate corresponding 3-hydroxy derivatives. The small GTPase proteins Rac2, Cdc42, and Rap1A are involved in the assembly and activation of the NADPH oxidase. This system is arranged vectorially in the phagosome membrane so that electrons pass through it from the NADPH-oxidizing site to the O2- reducing site, resulting in the production of superoxide anion and, consequently, the generation of reactive oxygen species such as H2O2, ONOO–, and HOCl. The biological importance of quorum-sensing communication in bacterial pathogens and fair understanding of the general molecular mechanisms have significantly propelled our effort in searching for effective quorum-quenching mechanisms.
Schematic representation of the AHL-dependent quorum-sensing system in gram-negative bacteria. The critical processes in quorum-sensing communication that could be targeted by quorum-quenching approaches are indicated. I, the LuxI-type AHL synthase; R, the LuxR-type transcription factor; triangle, AHL signals.
Schematic representation of enzymatic reactions of various quorum-sensing signal degradation and modification enzymes. (A) AHL signal inactivation, where R represents either 3-oxo substituent or absence of substitution. (B) AIP signal inactivation by the reactive oxygen or nitrogen intermediates generated by NADPH oxidase complex.
List of AHL quorum-quenching enzymes and antibody