Transcriptome analysis of mvaT and mvaU double knockout mutant of Pseudomonas aeruginosa PAO1
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ABSTRACT:
ORGANISM(S): Pseudomonas aeruginosa PAO1 Pseudomonas aeruginosa
PROVIDER: GSE135506 | GEO | 2019/08/08
REPOSITORIES: GEO
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Project description:The H-NS-like proteins MvaT and MvaU act coordinately as global repressors in Pseudomonas aeruginosa by binding to AT-rich regions of the chromosome. Although cells can tolerate the loss of either protein, identifying their combined regulatory effects has been challenging because the loss of both proteins is lethal due to induction of prophage Pf4 and subsequent superinfection of the cell. In other bacteria, H-NS promotes cellular fitness by inhibiting intragenic transcription from AT-rich target regions, preventing them from sequestering RNA polymerase; however, it is not known if whether MvaT and MvaU function similarly. Here we utilize a parental strain that cannot be infected by Pf4 phage to define the collective MvaT and MvaU regulon and demonstrate that the combined loss of both MvaT and MvaU leads to increased intragenic transcription from loci directly controlled by these proteins. We further show that the loss of MvaT and MvaU leads to a striking redistribution of RNA polymerase containing σ70 to genomic regions vacated by these proteins. Our findings suggest that the ability of H-NS-like proteins to repress intragenic transcription is a universal function of these proteins and point to a second mechanism by which MvaT and MvaU may contribute to the growth of P. aeruginosa.
2020-12-23 | GSE155024 | GEO
Project description:The H-NS-like proteins MvaT and MvaU act coordinately as global repressors in Pseudomonas aeruginosa by binding to AT-rich regions of the chromosome. Although cells can tolerate the loss of either protein, identifying their combined regulatory effects has been challenging because the loss of both proteins is lethal due to induction of prophage Pf4 and subsequent superinfection of the cell. In other bacteria, H-NS promotes cellular fitness by inhibiting intragenic transcription from AT-rich target regions, preventing them from sequestering RNA polymerase; however, it is not known if whether MvaT and MvaU function similarly. Here we utilize a parental strain that cannot be infected by Pf4 phage to define the collective MvaT and MvaU regulon and demonstrate that the combined loss of both MvaT and MvaU leads to increased intragenic transcription from loci directly controlled by these proteins. We further show that the loss of MvaT and MvaU leads to a striking redistribution of RNA polymerase containing σ70 to genomic regions vacated by these proteins. Our findings suggest that the ability of H-NS-like proteins to repress intragenic transcription is a universal function of these proteins and point to a second mechanism by which MvaT and MvaU may contribute to the growth of P. aeruginosa.
2020-12-23 | GSE155023 | GEO
Project description:It has been shown that the filamentous phage, Pf4, plays an important role in biofilm development, stress tolerance, genetic variant formation and virulence in Pseudomonas aeruginosa PAO1. These behaviours are linked to the appearance of superinfective phage variants. Here, we have investigated the molecular mechanism of superinfection as well as how the Pf4 phage can control host gene expression to modulate host behaviours. Pf4 exists as a prophage in PAO1 and encodes a homolog of the P2 phage repressor C. Through a combination of molecular techniques, ChIPseq and transcriptomic analyses, we show that repressor C (Pf4r) is the minimal factor for immunity against reinfection by Pf4 possibly through Pf4r binding to its putative promoter region, and that Pf4r also functions as a transcriptional regulator for expression of host genes. A binding motif for Pf4r was also identified. In wild type P. aeruginosa and Pfr4 complemented Pf4 deficient mutant strains, virulence factor related genes including phenazine and type VI secretion system effectors were upregulated, potentially explaining the reduced virulence of Pf4-deficient P. aeruginosa PAO1. X-ray crystal structure analysis shows that Pf4r forms symmetric homo-dimers homologous to the E.coli bacteriophage P2 RepC protein. A mutation associated with the superinfective Pf4r variant, found at the dimer interface, suggests dimer formation may be disrupted, which derepresses phage replication. This is supported by MALS analysis where the Pf4r* protein only shows monomer formation. Collectively, these data suggest the mechanism by which filamentous phages play such an important role in P. aeruginosa biofilm development.
2021-01-31 | GSE154459 | GEO
Project description:Pf4 is a filamentous bacteriophage integrated as a prophage into the genome of Pseudomonas aeruginosa PAO1. Pf4 virions can be produced without killing P. aeruginosa. Cell lysis can however occur during superinfection when Pf virions successfully infect a host lysogenized by a Pf superinfective variant. We have previously shown that infection of P. aeruginosa PAO1 with a superinfective Pf4 variant led to abolish twitching motility and to alter biofilm’s architecture. More precisely, the cells embedded into the biofilm were showing for most of them a filamentous morphology, that could be related to the activation of the cell envelope stress response involving both the AlgU and SigX extra cytoplasmic function sigma factors. Herein, we show that Pf4 variant-infection resulted also into a drastic dysregulation of 3,360 genes representing about 58% of P. aeruginosa’s genome, of which about 43% of the virulence factors encoding genes showing a down-regulation. Accordingly, Pf4 variant infection (termed Pf4*) causes in vivo reduction of P. aeruginosa virulence, decreased production of N-acyl-homoserine lactones and 2-alkyl-4-quinolones quorum sensing molecules, and related virulence factors, such as pyocyanin, elastase, and pyoverdine. In addition to virulence encoding genes, expression of genes involved in metabolism, including energy generation and iron homeostasis, was affected, suggesting further relationships between virulence and central metabolism. Altogether, these data suggest that Pf4 phage variant infection results in complex networks dysregulations, leading to reducing acute virulence in P. aeruginosa. This work contributes to the comprehension of the bacterial response to filamentous phage infection.
2022-07-05 | GSE201738 | GEO
Project description:In this study, we present a novel transcriptional regulator, PA1226, which modulates biofilm formation and virulence in P. aeruginosa. Mutation in this regulator abolished the ability of P. aeruginosa to produce biofilm in vitro, without any effect on the planktonic growth. This regulator is essential to the in vivo fitness and pathogenesis in both Drosophila melanogaster and BALB/c mouse lung infection models. Transcriptome analysis revealed that PA1226 regulates many essential virulence genes/pathways, including alginate, pili, and LPS biosynthesis.
2018-06-30 | GSE107640 | GEO
Project description:Pao extract is an herbal preparation of the bark of an amazonian rain forest tree,Pao Pereira (Geissospermum vellosii),which could inhibit Benign prostatic hyperplasia (BPH).Characterizing the molecular alterations of BPH1 and WPMY-1 cells treated with PAO is important for understanding the molecular mechanisms of PAO inhibiting BPH. We used microarrays to detail the RNA expression.
2020-06-01 | GSE128856 | GEO
Project description:Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms(1). Platelet factor 4 (PF4) is a platelets-secreted chemokine that can be activated by physical exercise. Recent studies showed that PF4 could improve cognition in aged mice(2), though whether it influences other neurological functions is vague. Here we investigated the role of PF4 in PD and normal aging mice. Intravenous administration of exogenous PF4 ameliorated both motor and non-motor symptoms of MPTP-induced PD mice, accompanying with reduced loss of nigrostriatal dopaminergic neurons and attenuated neuroinflammation in these regions. RNA sequencing showed that pathways related to inflammation were suppressed by PF4, which were confirmed by qPCR and immunohistochemical analysis. More interestingly, PF4 can also ameliorate the motor and non-motor symptoms after the loss of nigrostriatal dopaminergic neurons, and the efficacy can last for 3 weeks after PF4 administration. In addition, an improvement of motor performance and mood by PF4 was also observed in aged but not young mice. Collectively, our results show the potential of PF4 that not only be a therapeutic candidate for PD patients, but also be an option for aged people to improve their neurological performance.
2024-10-28 | GSE280106 | GEO
Project description:Platelet factors regulate wound healing and also signal from the blood to the brain. However, whether platelet factors modulate cognition, a highly valued and central manifestation of brain function, is unknown. Here, we show that systemic platelet factor 4 (PF4) modulates cognition and its molecular signature. Klotho, a longevity and cognition-enhancing protein, acutely activated platelets and increased circulating platelet factors, most robustly platelet factor 4 (PF4). To directly test PF4 effects on the brain, we treated mice with vehicle or systemic PF4. In young mice, PF4 enhanced synaptic plasticity and cognition. In aging mice, PF4 restored cognitive deficits and rejuvenated a molecular signature of cognition in the aging hippocampus. Augmenting platelet factors such as PF4, a possible messenger of klotho, may enhance cognition in the young brain and rejuvenate cognitive deficits in the aging brain.
2023-06-24 | GSE171929 | GEO
Project description:Background Small colony variants (SCVs) are slow-growing bacteria, which often show increased resistance to antibiotics and cause latent or recurrent infections. It is therefore important to understand the mechanisms at the basis of this phenotypic switch. Methodology/Principal findings One SCV (termed PAO-SCV) was isolated, showing high resistance to gentamicin and to the cephalosporine cefotaxime. PAO-SCV was prone to reversion as evidenced by emergence of large colonies with a frequency of 10-5 on media without antibiotics while it was stably maintained in presence of gentamicin. PAO-SCV showed a delayed growth, defective motility, and strongly reduced levels of the quorum sensing Pseudomonas quinolone signal (PQS). Whole genome expression analysis further suggested a multi-layered antibiotic resistance mechanism, including simultaneous over-expression of two drug efflux pumps (MexAB-OprM, MexXY-OprM), the LPS modification operon arnBCADTEF, and the PhoP-PhoQ two-component system. Conversely, the genes for the synthesis of PQS were strongly down-regulated in PAOSCV. Finally, genomic analysis revealed the presence of mutations in phoP and phoQ genes as well as in the mexZ gene encoding a repressor of the mexXY and mexABoprM genes. Only one mutation occurred only in REV, at nucleotide 1020 of the tufA gene, a paralog of tufB, both encoding the elongation factor Tu, causing a change of the rarely used aspartic acid codon GAU to the more common GAC, possibly causing an increase of tufA mRNA translation. High expression of phoP and phoQ was confirmed for the SCV variant while the revertant showed expression levels reduced to wild-type levels. Conclusions By combining data coming from phenotypic, gene expression and proteome analysis, we could demonstrate that resistance to aminoglycosides in one SCV mutant is multifactorial including overexpression of efflux mechanisms, LPS modification and is accompanied by a drastic down-regulation of the Pseudomonas quinolone signal quorum sensing system. We used microarrays to study changes in gene expression during early and late stationary phase of SCV and WT strains. SCV and WT cultures were grown in triplicate until early (24h) and late (48h) stationary phase. RNA was extracted, labelled and hybridised on Affymetrix P. aeruginosa expression microarrays.
2011-12-06 | E-GEOD-34141 | biostudies-arrayexpress
Project description:mRNA microarray analysis of bone marrow derived macrophages treated under four conditions, including Naïve (N). Bone marrow derived macrophages (BMDM) were derived from the bone marrow of mice and cultured in the presence of PAO, IFN-gamma, or lipopolysaccharide (LPS). Profiled groups include Naive, LPS, IFN, PAO. Compared each of the groups (PAO, LPS, IFN) with Naïve group.
2013-08-08 | E-GEOD-48609 | biostudies-arrayexpress