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PROVIDER: PRJNA1293920 | ENA |
REPOSITORIES: ENA
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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:Hafnia alvei H4 is a bacteria subject to regulation by N-acyl-l-homoserine lactone (AHL)-mediated quorum sensing system and is closely related to the corruption of instant sea cucumber. Studying the effect of Hafnia alvei H4 quorum sensing regulatory genes on AHLs is necessary for the quality and preservation of instant sea cucumber. In this study, the draft genome of H. alvei H4, which comprises a single chromosome of 4,687,151 bp, was sequenced and analyzed and the types of AHLs were analyzed employing thin-layer chromatography (TLC) and LC-MS/MS. Then the wild-type strain of H. alvei H4 and the luxI/R double mutant (ΔluxIR) were compared by transcriptome sequencing (RNA-seq). The results indicate that the incomplete genome sequence revealed the presence of one quorum-sensing (QS) gene set, designated as lasI/expR. Three major AHLs, N-hexanoyl-L-homoserine lactone (C6-HSL), N-butyryl-L-homoserine lactone (C4-HSL), and N-(3-oxo-octanoyl)-L-homoserine lactone (3-oxo-C8-HSL) were found, with C6-HSL being the most abundant. C6-HSL was not detected in the culture of the luxI mutant (ΔluxI) and higher levels of C4-HSL was found in the culture of the luxR mutant (ΔluxR), which suggested that the luxR gene may have a positive effect on C4-HSL production. It was also found that AHL and QS genes are closely related in the absence of luxIR double deletion. The results of this study can further elucidate at the genetic level that luxI and luxR genes are involved in the regulation of AHL.
2019-10-10 | GSE137815 | GEO
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: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:Pseudomonas aeruginosa is a major cause of nosocomial infections and also leads to severe exacerbations in cystic fibrosis or chronic obstructive pulmonary disease. Three intertwined quorum sensing systems control virulence of P. aeruginosa, with the rhl circuit playing the leading role in late and chronic infections. The majority of traits controlled by rhl transcription factor RhlR depend on PqsE, a dispensable thioesterase in Pseudomonas Quinolone Signal (PQS) biosynthesis that interferes with RhlR through an enigmatic mechanism likely involving direct interaction of both proteins. Here we show that PqsE and RhlR form a 2:2 protein complex that, together with RhlR agonist N-butanoyl-L-homoserine lactone (C4-HSL), solubilizes RhlR and thereby renders the otherwise insoluble transcription factor active. We determined crystal structures of the complex and identified residues essential for the interaction. To corroborate the chaperone like activity of PqsE, we designed stability-optimized variants of RhlR that bypass the need for C4-HSL and PqsE in activating PqsE/RhlR-controlled processes of P. aeruginosa. Together, our data provide insight into the unique regulatory role of PqsE and lay groundwork for developing new P. aeruginosa-specific pharmaceuticals.
2023-03-11 | PXD038000 | Pride
Project description:Comparison of a quorum sensing null mutant supplemented with C18-HSL, C18en-HSL, C18dien-HSL with D. shibae wild-type in order to identify traits induced by distinct autoinducers in this organism. Loop-design, two to three biological replicates of D. shibae wild-type, delta-luxI1 and delta-luxI1 supplemented with 500 nM C18-HSL, C18en-HSL and C18dien-HSL at cultivation start. Samples were taken in mid-exponential growth phase at OD600 0.4
2012-11-03 | E-GEOD-42010 | biostudies-arrayexpress
Project description:The Aspergillus fumigatus sterol regulatory element binding protein (SREBP) SrbA belongs to the basic Helix-Loop-Helix (bHLH) family of transcription factors and is crucial for antifungal drug resistance and virulence. The latter phenotype is especially striking, as loss of SrbA results in complete loss of virulence in murine models of invasive pulmonary aspergillosis (IPA). How fungal SREBPs mediate fungal virulence is unknown, though it has been suggested that lack of growth in hypoxic conditions accounts for the attenuated virulence. To further understand the role of SrbA in fungal infection site pathobiology, chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) was used to identify genes under direct SrbA transcriptional regulation in hypoxia. These results confirmed the direct regulation of ergosterol biosynthesis and iron uptake by SrbA in hypoxia and revealed new roles for SrbA in nitrate assimilation and heme biosynthesis. Moreover, functional characterization of an SrbA target gene with sequence similarity to SrbA identified a new transcriptional regulator of the fungal hypoxia response and virulence, SrbB. SrbB co-regulates genes involved in heme biosynthesis and demethylation of C4 sterols with SrbA in hypoxic conditions. However, SrbB also has regulatory functions independent of SrbA including regulation of carbohydrate metabolism. Loss of SrbB markedly attenuates A. fumigatus virulence, and loss of both SREBPs further reduces in vivo fungal growth. These data suggest that both A. fumigatus SREBPs are critical for hypoxia adaptation and virulence and reveals new insights into SREBPM-bM-^@M-^Ys complex role in infection site adaptation and fungal virulence. 4 hour and 12 hour ChIP experiments were completed. Input control samples for each set were collected.
2014-10-03 | E-GEOD-61974 | biostudies-arrayexpress
Project description:Comparison of a quorum sensing null mutant supplemented with C18-HSL, C18en-HSL, C18dien-HSL with D. shibae wild-type in order to identify traits induced by distinct autoinducers in this organism.
2012-11-03 | GSE42010 | GEO
Project description:Quorum sensing is a term used to describe cell-to-cell communication that allows cell density-dependent gene expression. Many Gram-negative bacteria use acyl-homoserine lactone (acyl-HSL) synthases to generate fatty acyl-HSL quorum sensing signals, which function with signal receptors to control expression of specific genes. The fatty acyl group is derived from fatty acid biosynthesis and provides signal specificity, but the variety of signals is limited. We have discovered that the photosynthetic bacterium Rhodopseudomonas palustris uses an acyl-HSL synthase to produce p-coumaroyl-HSL by using environmental p-coumaric acid rather than fatty acids from cellular pools. The bacterium has a signal receptor with homology to fatty acyl-HSL receptors that responds to p-coumaroyl-HSL to regulate global gene expression. We also found that p-coumaroyl-HSL is made by other bacteria including Bradyrhizobium BTAi1 and Silicibacter pomeroyi DSS-3. This discovery extends the range of possibilities for acyl-HSL quorum sensing and raises fundamental questions about quorum sensing within the context of environmental signaling. Keywords: Comparison of transcriptome profiles
2008-07-25 | GSE10642 | GEO