Quorum Sensing/Quorum Quenching in Acinetobacter baumannii clinical strains
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ABSTRACT:
ORGANISM(S): Acinetobacter baumannii
PROVIDER: GSE87009 | GEO | 2017/06/12
SECONDARY ACCESSION(S): PRJNA343222
REPOSITORIES: GEO
Similar Datasets
Project description:The human opportunistic pathogen Pseudomonas aeruginosa orchestrates the expression of many genes in a cell density-dependent manner by using a molecular communication system referred to as quorum sensing (QS). This bacterium uses an intricate network of regulators and QS molecules known as autoinducers. Among these autoinducers are two acyl-homoserine lactones (AHL) involved in QS circuits which modulate virulence factors production, biofilm formation, and antimicrobial sensitivity. Disrupting QS, a strategy referred to as quorum quenching (QQ), is a promising approach to modulate virulence while not directly challenging bacterial survival. For P. aeruginosa, QQ can be achieved using exogenous AHL-degrading lactonases. However, the importance of enzyme specificity on quenching efficacy has never been investigated. Here, we used two lactonases both targeting the signal molecules N-(3-oxododecanoyl)-L-Homoserine lactone (3-oxo-C12 HSL) and butyryl-homoserine lactone (C4 HSL) albeit with different efficacy on C4 HSL. Interestingly, both lactonases similarly decreased the concentrations of AHL and comparably impacted the expression of AHL-based circuits. Conversely, strong variations were observed in Pseudomonas Quinolone Signal (PQS) regulation. Both lactonases were then found to decrease virulence factors production and biofilm formation in vitro, albeit with different efficiencies. Unexpectedly, only the lactonase with substrate preference for 3-oxo-C12 HSL was able to inhibit P. aeruginosa pathogenicity in vivo in an amoeba infection model. Similarly, large variations between lactonases were observed in proteins involved in antibiotic resistance, biofilm formation, virulence and diverse cellular mechanisms. This global analysis provides the first evidence that QQ enzyme specificity is crucial to modulate QS-associated behavior in P. aeruginosa PA14.
2020-05-27 | PXD017421 | Pride
Project description:Quorum-sensing (QS) is a cell-cell communication system that controls gene expression in many bacterial species, mediated by diffusible signal molecules. While the intracellular regulatory mechanisms of QS are often well-understood, the functional roles of QS remain controversial. In particular, the use of multiple signals by many bacterial species poses a serious challenge to current functional theories. Here we address this challenge by showing that bacteria can use multiple QS signals to infer both their social (density) and physical (mass-transfer) environment. Analytical and evolutionary simulation models show that the detection of and response to complex social/physical contrasts requires multiple signals with distinct half-lives and combinatorial (non-additive) responses to signal concentrations. We test these predictions using the opportunistic pathogen Pseudomonas aeruginosa, and demonstrate significant differences in signal decay between its two primary signal molecules as well as diverse combinatorial responses to dual signal inputs. QS is associated with the control of secreted factors, and we show that secretome genes are preferentially controlled by synergistic M-bM-^@M-^XAND-gateM-bM-^@M-^Y responses to multiple signal inputs, ensuring the effective expression of secreted factors in high density and low mass-transfer environments. Our results support a novel functional hypothesis for the use of multiple signals and, more generally, show that bacteria are capable of combinatorial communication. The two primary signal molecules of P. aeruginosa are the homoserine lactones N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL) and N-butyryl-homoserine lactone (C4-HSL). Effects of the different signal molecules was assessed using a double QS synthase mutant of Pseudomonas aeruginosa PAO1 lasI/rhlI grown at 37M-BM-0C in 25 ml LB broth and 250 ml flasks with shaking at 200 r.p.m. in four treatments, each with a replicate: (a) no addition; (b) 3-oxo- C12-HSL; (c) C4-HSL; and (d) both 3-oxo-C12-HSL and C4-HSL.
2014-03-04 | E-GEOD-55110 | biostudies-arrayexpress
Project description:The common opportunistic human pathogen Pseudomonas aeruginosa employs quorum sensing QS to regulate a large set of genes involved in virulence and host-pathogen interactions. The Las circuit positioned on the top of the QS hierarchy in P. aeruginosa, makes use of N-acyl-L-homoserine lactones (AHL) as signal molecules, like N-3-oxo-dodecanoyl-L-homoserine lactone (3O-C12-HSL). Here, a quantitative proteomic approach was used to study the effect of natural 3O-C12-HSL and four AHL analogues on the expression and excretion of QS-regulated extracellular proteins. Treatment with AHL compounds resulted in significant difference in appearance of the 3O-C12-HSL-responsive reference proteins related to QS communication and virulence, i.e., a distinct activity as QS modulators. In summary, 3O-C12-HSL has a profound effect on extracellular proteome involved in the pathogenicity of P. aeruginosa, and the four AHL analogues have achieved a distinct inhibitory effect on the extracellular proteome.
2023-10-06 | PXD045881 | Pride
Project description:Candida auris occupies similar niches in various infections as Pseudomonas aeruginosa; however, the details of their interspecies communication remain largely unknown. To gain deeper insights into this bacterial–fungal relationship, phenotypic and transcriptomic analyses were conducted in the presence of the primary P. aeruginosa quorum-sensing molecule, 3-oxo-C12-homoserine lactone (HSL), against C. auris, with the results compared to those of C. albicans. We demonstrated a significant HSL-induced reduction in adhesion of C. auris cells at 100- and 200-μM concentrations. Furthermore, HSL exposure reduced intracellular iron and zinc levels and modulated C. auris metabolism toward beta-oxidation, which may be associated with the observed reduction in in vivo virulence at lower HSL concentrations compared with C. albicans. RNA-sequencing transcriptome analysis revealed 67 and 306 upregulated genes, as well as 111 and 168 downregulated genes, in response to 100 and 200 μM HSL, respectively. We identified 45 overlapping upregulated and 25 overlapping downregulated genes between the two HSL concentrations. Our findings indicate that HSL-induced effects are not specific to C. albicans; additionally, several characteristics are present in C. auris but not in C. albicans following HSL exposure. Similar to other Candida-derived C12 compounds (e.g., farnesol), HSL reduces several C. auris survival strategies, which may significantly influence the nature of P. aeruginosa–C. auris co-habitation.
2024-07-10 | GSE271513 | GEO
Project description:In this report, we investigated oxo-C14-HSL-interacting proteins in plants. We propose the AHL-Interacting Protein 1 (ALI1) (previously known as AtGalk2) as interacting protein for oxo-C14-HSL in Arabidopsis. We present here several levels of confirmation and suggest that ALI1 is required for the perception of oxo-C14-HSL in Arabidopsis. This is the first direct evidence of a plant protein interacting with a bacterial quorum sensing molecule.
2020-12-20 | GSE156726 | GEO
Project description:In order to gain coherent insights into plant responses we performed transcriptional analysis of Arabidopsis seedling after treatment with three different AHLs: N-hexanoyl-L-homoserine lactone (C6-HSL), N-3-oxo-decanoyl-L-homoserine lactone (oxo-C10-HSL), and N-3-oxo-tetradecanoyl-L-homoserine lactone (oxo-C14-HSL). Furthermore, we analyzed the transcriptome of oxo-C14-HSL pretreated plants after a secondary challenge with 100 nM flg22 for 2 and 24 hours after treatment. Gene expression in Arabidopsis thaliana seedlings were measured after a 3-days-pretreatment with 6 µM of three different N-acyl homoserine lactones in comparison to plants treated with the coresponding volume of acetone (solvent control). Plants pretreated with oxo-C14-HSL were in addition treated with 100nM of flg22 to induced defense response. Three independent experiments were performed (replicates).
2014-11-26 | E-GEOD-52979 | biostudies-arrayexpress
Project description:Analysis of the effect of a bacterial quorum sensing molecule on in-vitro culture of human endothelial cells at gene expression levels. Objective: Chronic infection has long been postulated as a stimulus for atherogenesis. Pseudomonas aeruginosa infection has been associated with increased atherosclerosis in rats, and the bacteria produce a quorum sensing molecule 3-oxo-dodecynoyl-homoserine lactone (3OC12-HSL) that is critical for colonization and virulence. Paraoxonase 2 (PON2) hydrolyzes 3OC12-HSL and also protects against the effects of oxidized phospholipids thought to contribute to atherosclerosis. We now report the response of human aortic endothelial cells (HAEC) to 3OC12-HSL and oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (Ox-PAPC) in relation to PON2 expression. Methods and Results: Using expression profiling and network modeling, we identified the unfolded protein response (UPR), cell cycle genes, and the MAPK signaling pathway to be heavily involved in the HAEC response to 3OC12-HSL. The network also showed striking similarities to a network created based on HAEC response to Ox-PAPC, a major component of minimally-modified LDL. HAEC in which PON2 was silenced by siRNA showed increased pro-inflammatory and UPR responses when treated with 3OC12-HSL or Ox-PAPC. Conclusion: 3OC12-HSL and Ox-PAPC influence similar inflammatory pathways. Quorum sensing molecules such as 3OC12-HSL contribute to the pro-atherogenic effects of chronic infection and the anti-atherogenic effects of PON2 include destruction of quorum sensing molecules. 4 HAEC lines from different donors were treated with 3-O-C12 HSL or control (medium).
2010-12-30 | E-GEOD-26295 | biostudies-arrayexpress
Project description:Transcriptional response of the QS-negative D. shibae strain ∆luxI1 towards externally added 500nM autoinducer (AI) 3-oxo-C14-HSL over a time period of 3 hours.
2018-11-03 | GSE122111 | GEO
Project description:We examined whether the budding yeast Saccharomyces cerevisiae can sense chemical signals from prokaryotes, specifically a variety of quorum sensing molecules from different bacteria species and from Candida albicans. We found that only N-acyl-3-oxo-dodecanoyl homoserine lactone (C12) from the opportunistic human pathogen Pseudomonas aeruginosa induces a stress response in yeast. Microarray experiments were performed in order to continue investigating the stress response. We treated S. cerevesiae (WT strain W303) with N-(3-oxo-dodecanoyl) homoserine lactone (C12), a quorum sensing molecule of Pseudomonas aeruginosa, which we found causes a stress response using a GFP reporter for HSP-12. Treatment conditions: 100 uM C12, 100 uM C12-lactam (control: synthetic analogue of C12 that is inactive in P. aeruginosa), DMSO (control: solvent), and 0.3 mM H2O2 (for comparison to oxidative stress).
2020-03-02 | E-MTAB-4802 | biostudies-arrayexpress
Project description:In order to gain coherent insights into plant responses we performed transcriptional analysis of Arabidopsis seedling after treatment with three different AHLs: N-hexanoyl-L-homoserine lactone (C6-HSL), N-3-oxo-decanoyl-L-homoserine lactone (oxo-C10-HSL), and N-3-oxo-tetradecanoyl-L-homoserine lactone (oxo-C14-HSL). Furthermore, we analyzed the transcriptome of oxo-C14-HSL pretreated plants after a secondary challenge with 100 nM flg22 for 2 and 24 hours after treatment.
2014-11-26 | GSE52979 | GEO