Pseudomonas aeruginosa PAK
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ABSTRACT:
PROVIDER: PRJNA491608 | ENA |
REPOSITORIES: ENA
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Project description:Polymyxins are the last-line antibiotics against multidrug-resistant Pseudomonas aeruginosa however, resistance to polymyxins has been increasingly reported. Therefore, understanding the mechanisms of polymyxin activity and resistance is crucial for preserving their clinical usefulness. This study employed comparative metabolomics and transcriptomics to investigate the responses of polymyxin-susceptible PAK (polymyxin B MIC 1 mg/l) and its polymyxin-resistant pmrB mutant PAKpmrB6 (MIC 16 mg/l) to polymyxin B (4, 8, and 128 mg/l) at 1, 4, and 24h. Our results revealed that polymyxin B at 4 mg/l induced different metabolic and transcriptomic responses between polymyxin-susceptible and -resistant P. aeruginosa. In PAK, polymyxin B significantly activated PmrAB and the mediated arn operon, leading to increased 4-amino-4-deoxy-L-arabinose (L-Ara4N) synthesis and the addition to lipid A. On the contrary, polymyxin B did not increase lipid A modification in PAKpmrB6. Moreover, the syntheses of lipopolysaccharide and peptidoglycan were significantly decreased in PAK, but increased in PAKpmrB6 due to polymyxin B treatment. In addition, 4 mg/l polymyxin B significantly perturbed phospholipid and fatty acid levels and induced oxidative stress in PAK, but not in PAKpmrB6. Notably, the increased trehalose-6-phosphate levels indicate that polymyxin B potentially caused osmotic imbalance in both strains. Furthermore, 8 and 128 mg/l polymyxin B significantly elevated lipoamino acid levels and decreased phospholipid levels, but without dramatic changes in lipid A modification in both wildtype and mutant strains. Overall, this systems study is the first to elucidate the complex and dynamic interactions of multiple cellular pathways associated with polymyxin mode of action against P. aeruginosa.
2018-11-14 | MTBLS751 | MetaboLights
Project description:Background: Pseudomonas aeruginosa often causes multidrug-resistant infections in immunocompromised patients and polymyxins are often used as the last-line therapy. Alarmingly, resistance to polymyxins has been increasingly reported worldwide recently. To rescue this last-resort class of antibiotics, it is necessary to systematically understand how P. aeruginosa alters its metabolism in response to polymyxin treatment, thereby facilitating the development of effective therapies. To this end, a genome-scale metabolic model (GSMM) was employed to analyse bacterial metabolic changes at the systems level. Findings: A high-quality GSMM iPAO1 was constructed for P. aeruginosa PAO1 for antimicrobial pharmacological research. Model iPAO1 encompasses an additional periplasmic compartment and contains 3,022 metabolites, 4,265 reactions and 1,458 genes in total. Growth prediction on 190 carbon and 95 nitrogen sources achieved an accuracy of 89.1%, outperforming all reported P. aeruginosa models. Notably, prediction of the essential genes for growth achieved a high accuracy of 87.9%. Metabolic simulation showed that lipid A modifications associated with polymyxin resistance exert a limited impact on bacterial growth and metabolism, but remarkably change the physiochemical properties of the outer membrane. Modelling with transcriptomics constraints revealed a broad range of metabolic responses to polymyxin treatment, including reduced biomass synthesis, upregulated amino acids catabolism, induced flux through the tricarboxylic acid cycle, and increased redox turnover. Conclusions: Overall, iPAO1 represents the most comprehensive GSMM constructed to date for Pseudomonas. It provides a powerful systems pharmacology platform for the elucidation of complex killing mechanisms of antibiotics.
2018-02-28 | MTBLS630 | MetaboLights
Project description:Pseudomonas aeruginosa T3SS screen
| PRJNA849930 | ENA
Project description:Pseudomonas aeruginosa PAK Genome sequencing
| PRJNA232360 | ENA
Project description:Pseudomonas aeruginosa PAK genome sequencing project
| PRJNA66135 | ENA
Project description:Pseudomonas aeruginosa PAK Raw sequence reads
| PRJNA311263 | ENA
Project description:Due to the rising incidence of antibiotic resistant infections, last-line antibiotics polymyxins have resurged in the clinics together with the appearance of new bacterial strategies of escape. The Gram-negative opportunistic pathogen Pseudomonas aeruginosa develops resistance to colistin/polymyxin by distinct molecular mechanisms, mostly involving the modification of the lipid A component of the LPS by proteins encoded within the arnBCDATEF-ugD (called arn) operon. We characterized a polymyxin-induced operon, named mipBA, present in P. aeruginosa group of strains devoid of the arn operon. Mass spectrometry-based quantitative proteomics showed that the absence of MipBA modifies the membrane proteome, notably impacting ParRS-regulated proteins, in response to polymyxin.
2024-01-12 | PXD043253 | Pride
Project description:The bacterial type III secretion system (TTSS) is dedicated to directly effect host cell pathways by pathogens. In order to identify the key host responses of the various parts of the TTSS, we utilized expression profiling of a lung pneumocytes cell line, A549, exposed to various isogenic mutant strains of Pseudomonas aeruginosa PAK. We have devised a novel filtering method to isolate the key responses to the effector proteins as well as the translocation machinery. Individually, the effector proteins elicited host responses that were consistent with the known function of each, many of which either regulated, or are regulated by the cell cycle. However, our analysis has shown that the effector proteins elicit a distinct host expression pattern when present in combination, suggesting that these proteins function in synergy. Furthermore, the host transcriptional response to the translocation complex involved genes that are involved in remodeling of the plasma membrane, suggesting that the host cell is able to sense the protrusion of the TTSS machinery. This study shows that the individual components of the TTSS define an integrated system and that a systems biology approach is required to fully understand the complex interplay between pathogen and host. Keywords = Pseudomonas aeruginosa Keywords = A549 human lung carcinoma cell line Keywords = cystic fibrosis Keywords: repeat sample
2004-12-10 | GSE1469 | GEO
Project description:Pseudomonas aeruginosa is a facultative human pathogen especially dangerous for immunocompromised patients. It is known from its high adaptability and complex regulatory systems involving huge repertoire of transcriptional regulators (TRs). The Lrp/AsnC family consists of proteins engaged mostly in regulation of processes such as amino acid metabolism but the function of most of them remains unknown. The aim of this study was characterization of the Lrp/AsnC-type regulator PA2577 of P. aeruginosa. Transcriptional profiling of P. aeruginosa PAO1161 overexpressing PA2577 revealed changes in mRNA level of 171 genes. Among downregulated loci PA2576 gene, encoding an EamA-like membrane transporter transcribed divergently to PA2577, was identified. ChIP-seq analysis together with EMSA analysis revealed binding site of PA2577 in PA2577/PA2576 intergenic region, indicating direct regulation of PA2576 expression by PA2577. PA2576 was shown to interact with PA5006 and PA3694 proteins predicted to be involved in membrane processes, especially LPS biosynthesis. Defects of growth of PA2577 and PA2576 deficient cells in conditions of polymyxin B supplementation was shown. Overall, presented data uncovered the regulatory properties of PA2577 acting as the repressor of divergently transcribed PA2576 gene, being a part of LPS biogenesis process in P. aeruginosa.
2021-12-10 | GSE186749 | GEO