Quorum sensing molecule N-(3-oxododecanoyl)-l-homoserine lactone: An all-rounder in mammalian cell modification

Guo, Jiajie; Yoshida, Kaya; Ikegame, Mika; Okamura, Hirohiko

doi:10.1016/j.job.2020.01.001

Cited by 18 publications

(12 citation statements)

References 128 publications

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“…Dendritic cells (DCs) stimulated by lipopolysaccharides and in the presence of 3-oxo-C12-HSL show a decrease in their proinflammatory cytokine such as IL-12 and interferon-γ (IFNγ) ( 51 – 53 ). However, reports on anti-inflammatory IL-10 are contradictory.…”

Section: Introductionmentioning

confidence: 99%

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

2020

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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.

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Section: Introductionmentioning

confidence: 99%

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

2020

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“…Mouse-specific gene clusters include genes involved in reproduction, olfaction, gustation, and host defense and immunity, like certain genes for MHC and G-protein-coupled receptors (Emes et al, 2003). When applied to mammalian cells, hydrophobic AHL can quickly diffuse across the plasma membrane via interaction with phospholipids (Davis et al, 2010) to access the cytoplasm, ER and mitochondria (Guo et al, 2020). The absorption of AHL into the host cells may further be enhanced by cell membrane extensions and protrusions, such as microvilli on the apical surface of differentiated polarized intestinal epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, 3O-C 12 -HSL has been demonstrated to influence mitochondrial physiology in fibroblasts by releasing cytochrome c via activating caspases 3/7 and 8 without the involvement of Bak/Bax regulators of apoptosis, i.e., having a pro-apoptotic effect (Schwarzer et al, 2014). 3O-C 12 -HSL may trigger apoptosis and cytotoxicity in many type of cells (Tateda et al, 2003;Schwarzer et al, 2012;Zhao et al, 2016;Neely et al, 2018) and this was recently reviewed (Guo et al, 2020). Still, fibroblasts and polarized human epithelial cells used in this study (Supplementary Figure S1) and earlier (Karlsson et al, 2012b;Losa et al, 2015) and human primary neutrophils and macrophages (Karlsson et al, 2012a;Holm et al, 2016), did not display any apoptotic changes or cell death in response to 3O-C 12 -HSL in the used conditions.…”

Section: Discussionmentioning

confidence: 99%

Pseudomonas aeruginosa N-3-Oxo-Dodecanoyl-Homoserine Lactone Impacts Mitochondrial Networks Morphology, Energetics, and Proteome in Host Cells

et al. 2020

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Mitochondria play crucial roles in cellular metabolism, signaling, longevity, and immune defense. Recent evidences have revealed that the host microbiota, including bacterial pathogens, impact mitochondrial behaviors and activities in the host. The pathogenicity of Pseudomonas aeruginosa requires quorum sensing (QS) cell-cell communication allowing the bacteria to sense population density and collectively control biofilm development, virulence traits, adaptation and interactions with the host. QS molecules, like N-3-oxo-dodecanoyl-L-homoserine lactone (3O-C 12-HSL), can also modulate the behavior of host cells, e.g., epithelial barrier properties and innate immune responses. Here, in two types of cells, fibroblasts and intestinal epithelial cells, we investigated whether and how P. aeruginosa 3O-C 12-HSL impacts the morphology of mitochondrial networks and their energetic characteristics, using high-resolution transmission electron microscopy, fluorescence live-cell imaging, assay for mitochondrial bioenergetics, and quantitative mass spectrometry for mitoproteomics and bioinformatics. We found that 3O-C 12-HSL induced fragmentation of mitochondria, disruption of cristae and inner membrane ultrastructure, altered major characteristics of respiration and energetics, and decreased mitochondrial membrane potential, and that there are distinct cell-type specific details of these effects. Moreover, this was mechanistically accompanied by differential expression of both common and cell-type specific arrays of components in the mitochondrial proteome involved in their structural organization, electron transport chain complexes and response to stress. We suggest that this effect of 3O-C 12-HSL on mitochondria may represent one of the events in the interaction between P. aeruginosa and host mitochondria and may have an impact on the pathogens strategy to hijack host cell activities to support their own survival and spreading.

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“…AHLs are known to influence gene expression and certain behaviors in eukaryotes, a phenomenon called interkingdom signaling [ 4 , 5 , 6 ]. To date, most studies on the effects of AHLs on mammal cells have focused on the well-known molecules 3-oxo-C12-HSL (1) and C4-HSL from the pathogenic bacteria Pseudomonas aeruginosa , and 3-oxo-C6-HSL from Vibrio fischeri for medical and historic reasons [ 7 , 8 , 9 , 10 ]. AHLs have been described to enter human cells, where they can exert various effects ranging from apoptosis induction to immune and inflammation modulation [ 7 , 8 , 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory Effects of Analogues of N-Acyl Homoserine Lactones on Eukaryotic Cells

Peyrottes

Coquant

Brot

et al. 2020

IJMS

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Background: Since acyl-homoserine lactone (AHL) profiling has been described in the gut of healthy subjects and patients with inflammatory bowel disease (IBD), the potential effects of these molecules on host cells have raised interest in the medical community. In particular, natural AHLs such as the 3-oxo-C12-HSL exhibit anti-inflammatory properties. Our study aimed at finding stable 3-oxo-C12-HSL-derived analogues with improved anti-inflammatory effects on epithelial and immune cells. Methods: We first studied the stability and biological properties of the natural 3-oxo-C12-HSL on eukaryotic cells and a bacterial reporter strain. We then constructed and screened a library of 22 AHL-derived molecules. Anti-inflammatory effects were assessed by cytokine release in an epithelial cell model, Caco-2, and a murine macrophage cell line, RAW264.7, (respectively, IL-8 and IL-6) upon exposure to the molecule and after appropriate stimulation (respectively, TNF-α 50 ng/mL and IFN-γ 50 ng/mL, and LPS 10 ng/mL and IFN-γ 20 U/mL). Results: We found two molecules of interest with amplified anti-inflammatory effects on mammalian cells without bacterial-activating properties in the reporter strain. The molecules furthermore showed improved stability in biological medium compared to the native 3-oxo-C12-HSL. Conclusions: We provide new bio-inspired AHL analogues with strong anti-inflammatory properties that will need further study from a therapeutic perspective.

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Quorum sensing molecule N-(3-oxododecanoyl)-l-homoserine lactone: An all-rounder in mammalian cell modification

Cited by 18 publications

References 128 publications

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

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

Pseudomonas aeruginosa N-3-Oxo-Dodecanoyl-Homoserine Lactone Impacts Mitochondrial Networks Morphology, Energetics, and Proteome in Host Cells

Anti-Inflammatory Effects of Analogues of N-Acyl Homoserine Lactones on Eukaryotic Cells

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