Project description:ErfA is a transcription factor of Pseudomonas aeruginosa. We here define the genome-wide binding sites of ErfA by DAP-seq in Pseudomonas aeruginosa PAO1 and IHMA87, Pseudomonas chlororaphis PA23, Pseudomonas protegens CHA0 and Pseudomonas putida KT2440.
Project description:Pseudomonas aeruginosa is a leading cause of hospital acquired infections for which the development of new antibiotics is urgently needed. Unlike most enteric bacteria, P. aeruginosa lacks thymidine kinase and thymidine phosphorylase activity, and thus cannot scavenge exogenous thymine. An appealing strategy to selectively target P. aeruginosa while leaving the healthy microbiome largely intact would thus be to disrupt thymidine synthesis while providing exogenous thymine. However, this approach was previously intractable because known antibiotics that perturb thymidine synthesis are largely inactive against P. aeruginosa. Here, we characterize a novel dihydrofolate reductase inhibitor, fluorofolin, that exhibits significant activity against P. aeruginosa in culture and in a mouse thigh infection model. Fluorofolin is active against a wide range of clinical P. aeruginosa isolates resistant to known antibiotics, including critical antibiotic development priorities expressing the beta-lactamases KPC-5 and NDM-1. Importantly, in the presence of thymine supplementation, fluorofolin activity is selective for P. aeruginosa. Resistance to fluorofolin can emerge through overexpression of the efflux pumps MexCD-OprJ and MexEF-OprN. However, these mutants also decrease pathogenesis, in part due to increased export of quorum sensing precursors leading to decreased virulence factor production. Our findings thus demonstrate how understanding species-specific genetic differences and discovery of an antibiotic with a widely conserved target can enable selective targeting of important pathogens while revealing new tradeoffs between resistance and pathogenesis.
Project description:To further determine the origin of the increased virulence of Pseudomonas aeruginosa PA14 compared to Pseudomonas aeruginosa PAO1, we report a transcriptomic approach through RNA sequencing. Next-generation sequencing (NGS) has revolutioned sistems-based analsis of transcriptomic pathways. The goals of this study are to compare the transcriptomic profile of all 5263 orthologous genes of these nearly two strains of Pseudomonas aeruginosa.
Project description:Analysis of a SigX knockout mutant of Pseudomonas aeruginosa H103 strain in minimal medium with glucose as carbon source (M9G). SigX, one of the 19 extra-cytoplasmic function sigma factors of P. aeruginosa, was only known to be involved in transcription of the gene encoding the major outer membrane protein OprF in Pseudomonas aeruginosa. Deletion of the ECF sigma factor sigX gene provide insights into the SigX role in several virulence and biofilm- related phenotypes in Pseudomonas aeruginosa.
Project description:Oberhardt2008 - Genome-scale metabolic
network of Pseudomonas aeruginosa (iMO1056)
This model is described in the article:
Genome-scale metabolic
network analysis of the opportunistic pathogen Pseudomonas
aeruginosa PAO1.
Oberhardt MA, Puchałka J, Fryer
KE, Martins dos Santos VA, Papin JA.
J. Bacteriol. 2008 Apr; 190(8):
2790-2803
Abstract:
Pseudomonas aeruginosa is a major life-threatening
opportunistic pathogen that commonly infects immunocompromised
patients. This bacterium owes its success as a pathogen largely
to its metabolic versatility and flexibility. A thorough
understanding of P. aeruginosa's metabolism is thus pivotal for
the design of effective intervention strategies. Here we aim to
provide, through systems analysis, a basis for the
characterization of the genome-scale properties of this
pathogen's versatile metabolic network. To this end, we
reconstructed a genome-scale metabolic network of Pseudomonas
aeruginosa PAO1. This reconstruction accounts for 1,056 genes
(19% of the genome), 1,030 proteins, and 883 reactions. Flux
balance analysis was used to identify key features of P.
aeruginosa metabolism, such as growth yield, under defined
conditions and with defined knowledge gaps within the network.
BIOLOG substrate oxidation data were used in model expansion,
and a genome-scale transposon knockout set was compared against
in silico knockout predictions to validate the model.
Ultimately, this genome-scale model provides a basic modeling
framework with which to explore the metabolism of P. aeruginosa
in the context of its environmental and genetic constraints,
thereby contributing to a more thorough understanding of the
genotype-phenotype relationships in this resourceful and
dangerous pathogen.
This model is hosted on
BioModels Database
and identified by:
MODEL1507180020.
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To the extent possible under law, all copyright and related or
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Project description:In the present study, we employed Affymetrix Pseudomonas aeruginosa GeneChip arrays to investigate global gene expression profiles during the cellular response of Pseudomonas aeruginosa to sodium hypochlorite Keywords: Antimicrobial response
Project description:Purpose: To uncover immune mediated genes and pathways by Pseudomonas aeruginosa infection that are modulated by the homeodomain PITX1/UNC-30, which plays a vital role in the GABAergic signaling in C. elegans Methods: RNA was extracted from synchronized Pseudomonas aeruginosa infected L4 stage unc-30(ok613) and WT using Qiagen extraction kits and following standard methods. The animals were grown on OP50 at 20 C and infected at 25 C. Results: RNA seq analyses shows enriched and signficant Pseudomonas aeruginosa mediated upregulated immune, neuropeptide and metabolism genes and pathways that are dependent of GABAergic signaling Conclusions: Our study uncovered GABAgergic signaling to be modulator of the innate immunity in C elegans during Pseudomonas aeruginosa infection
Project description:Arrays comparing Pseudomonas aeruginosa growth in a defined synthetic cystic fibrosis sputum medium with and without aromatic amino acids. Additional arrays comparing wild-type Pseudomonas aeruginosa and phhR mutant P. aeruginosa in defined synthetic cystic fibrosis sputum medium.
