The impaired quorum sensing response of MexAB-OprM efflux pump overexpressing mutants is not due to non-physiological efflux of 3-oxo-C12-HSL
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ABSTRACT:
PROVIDER: PRJNA644728 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12170566_1.fastq.gz | Fastqsanger.gz | |||
| SRR12170566_2.fastq.gz | Fastqsanger.gz | |||
| SRR12170567_1.fastq.gz | Fastqsanger.gz | |||
| SRR12170567_2.fastq.gz | Fastqsanger.gz | |||
| SRR12170568_1.fastq.gz | Fastqsanger.gz |
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Project description:Multidrug (MDR) efflux pumps are ancient and conserved molecular machineries with relevant roles in different aspects of the bacterial physiology, besides antibiotic resistance. In the case of the environmental opportunistic pathogen Pseudomonas aeruginosa, it has been shown that overexpression of different efflux pumps is linked to the impairment of the quorum sensing (QS) response. Nevertheless, the causes of such impairment are different for each analyzed efflux pump. Herein, we performed an in-depth analysis of the QS-mediated response of a P. aeruginosa antibiotic resistant mutant that overexpresses MexAB-OprM. Although previous work claimed that this efflux pump extrudes the QS signal 3-oxo-C12-HSL, we show otherwise. Our results evidence that the observed attenuation in the QS response when overexpressing this pump is related to an impaired production of alkyl quinolone QS signals, likely prompted by the reduced availability of one of their precursors, the octanoate. Together with previous studies, this indicates that, although the consequences of overexpressing efflux pumps are similar (impaired QS response), the underlying mechanisms are different. This ‘apparent redundancy' of MDR efflux systems can be understood as a P. aeruginosa strategy to keep the robustness of the QS regulatory network and modulate its output in response to different signals.
2021-10-25 | GSE153996 | GEO
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:We worked with microarrys analysis in presence of 3-oxo-C12-HSL molecule to analyze the profile of the genes implicated in the Quorum Quenching network in A.baumannii clinical strains. Interestingly, only 13 genes were overexpressed under 3-oxo-C12-HSL molecule being the most level a gene which encodes an Alpha/beta hydrolase enzyme (5.01). The 46.15% of the genes overexpressed were implicated in the synthesis of the acyl-homoserine lactones (AHLs).
2017-06-12 | GSE87009 | GEO
Project description:Repurposing bioactive aporphine alkaloids as efflux pump inhibitors
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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: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: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: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 study is about the role of Bacteroides thetaiotaomicron in the human gut microbiota, specifically its ability to form biofilms in response to bile salts. The study found that bile induces the expression of certain efflux pumps, and inhibiting these pumps impairs biofilm formation. Among the induced pumps, the BipABC pump is crucial for biofilm formation as it is involved in the efflux of magnesium, which affects the biofilm's extracellular matrix and structure. This discovery sheds light on how intestinal chemical cues, like bile salts, regulate biofilm formation in B. thetaiotaomicron, a significant gut symbiont.
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Project description:We used DNA microarrays to define the physiological roles of the Tap efflux pump in M. bovis BCG during the exponential and the stationary phase of in vitro growth. For this purpose we constructed a M. bovis BCG strain in which the tap gene was inactivated by the insertion of a hygromycin resistance cassette (Ω-hyg). When the gene expression patterns of the tap mutant were compared to the wild-type strain, almost no differences were observed during exponential growth; only seven genes slightly increased their expression. In contrast, more that 100 genes showed a variation in their level of expression during stationary growth. More than ten representative genes were chosen from the microarray experiments and their expression was measured by quantitative RT-PCR using sigA as invariant internal control. In support to the gene expression profiling data, the mRNA levels of all selected genes was significantly different in the tap mutant strain relative to control. A functional category analysis (http://tuberculist.epfl.ch/index.html) of the genes differentially expressed revealed a high proportion belonging to the Virulence, Detoxification, Adaptation (VDA), Intermediary Metabolism and Respiration (IMR), Conserved Hypotheticals (CH), and Cell Wall and Cell Processing (CWCP) categories suggesting a major adaptation to a stress generated by inactivation of the tap efflux pump gene.
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