Impact of N-Acyl-Homoserine Lactones, Quorum Sensing Molecules, on Gut Immunity

Abstract

Among numerous molecules found in the gut ecosystem, quorum sensing (QS) molecules represent an overlooked part that warrants highlighting. QS relies on the release of small molecules (auto-inducers) by bacteria that accumulate in the environment depending on bacterial cell density. These molecules not only are sensed by the microbial community but also interact with host cells and contribute to gut homeostasis. It therefore appears entirely appropriate to highlight the role of these molecules on the immune system in dysbiosis-associated inflammatory conditions where the bacterial populations are imbalanced. Here, we intent to focus on one of the most studied QS molecule family, namely, the type I auto-inducers represented by N- acyl-homoserine lactones (AHL). First described in pathogens such as Pseudomonas aeruginosa , these molecules have also been found in commensals and have been recently described within the complex microbial communities of the mammalian intestinal tract. In this mini-review, we will expound on this emergent field of research. We will first recall evidence on AHL structure, synthesis, receptors, and functions regarding interbacterial communication. Then, we will discuss their interactions with the host and particularly with agents of the innate and adaptive gut mucosa immunity. This will reveal how this new set of molecules, driven by microbial imbalance, can interact with inflammation pathways and could be a potential target in inflammatory bowel disease (IBD). The discovery of the general impact of these compounds on the detection of the bacterial quorum and on the dynamic and immune responses of eukaryotic cells opens up a new field of pathophysiology.

An Organ System-Based Synopsis ofPseudomonas aeruginosaVirulence

“…Again, these in vitro observations need to be interpreted with caution as non-physiological concentrations of oxo-C 12 -HSL were used in the studies using immortalized cell line. A more detailed review of modulation of gut immunity by QS molecules can be found here[ 376 ].…”

Binding site profiles and N-terminal minor groove interactions of the master quorum-sensing regulator LuxR enable flexible control of gene activation and repression

“…Many tiers of factors are assumed to govern the LuxR-centered QS output for various collective phenotypes, e.g. the upstream autoinducer signaling cascades of luxR expression, the DNA binding sites and their distribution in genes, and the manner by which LuxR interacts with specific DNA ( 45–48 ). Although further analysis of the signaling dynamics of the QS input is warranted, conserved QS components, such as LuxO, qrr s, and AphA, have been identified, demonstrating that V. alginolyticus harbors QS systems resembling that of V. harveyi ( 12 , 18 , 49 ).…”

On the Role of Paraoxonase-1, Chemokine (C-C motif) Ligand 2 and Metabolism in Oxidation, Inflammation and Disease. A 2021 Update

“…when the concentrations of signaling molecules reach a critical threshold, the result is modulation of certain target genes that trigger the formation of biofilms [37]. In Gram-negative bacteria, N-acyl-homoserine lactones (AHL) have been identified as the major signaling molecules in this communication system [38][39][40]. Considerable evidence suggests that PON1 plays an important role against biofilm formation.…”