Project description:Objectives: Colistin remains a last-line treatment for multidrug-resistant Acinetobacter baumannii and combined use of colistin and carbapenems has shown synergistic effects against multidrug-resistant strains. In order to understand the bacterial responses to these antibiotics we analysed the transcriptome of A. baumannii following exposure to each. Overall design: Methods: RNA sequencing was employed to determine changes in the transcriptome following treatment with colistin and doripenem, both alone and in combination, using an in vitro pharmacokinetics/pharmacodynamics (PK/PD) model to mimic the pharmacokinetics of both antibiotics in patients.
Project description:Kim2009 - Genome-scale metabolic network of
Acinetobacter baumannii (AbyMBEL891)
This model is described in the article:
network analysis and drug targeting of multi-drug resistant
pathogen Acinetobacter baumannii AYE.
Kim HU, Kim TY, Lee SY.
Mol Biosyst 2010 Feb; 6(2):
Acinetobacter baumannii has emerged as a new clinical threat
to human health, particularly to ill patients in the hospital
environment. Current lack of effective clinical solutions to
treat this pathogen urges us to carry out systems-level studies
that could contribute to the development of an effective
therapy. Here we report the development of a strategy for
identifying drug targets by combined genome-scale metabolic
network and essentiality analyses. First, a genome-scale
metabolic network of A. baumannii AYE, a drug-resistant strain,
was reconstructed based on its genome annotation data, and
biochemical knowledge from literatures and databases. In order
to evaluate the performance of the in silico model,
constraints-based flux analysis was carried out with
appropriate constraints. Simulations were performed from both
reaction (gene)- and metabolite-centric perspectives, each of
which identifies essential genes/reactions and metabolites
critical to the cell growth. The gene/reaction essentiality
enables validation of the model and its comparative study with
other known organisms' models. The metabolite essentiality
approach was undertaken to predict essential metabolites that
are critical to the cell growth. The EMFilter, a framework that
filters initially predicted essential metabolites to find the
most effective ones as drug targets, was also developed.
EMFilter considers metabolite types, number of total and
consuming reaction linkage with essential metabolites, and
presence of essential metabolites and their relevant enzymes in
human metabolism. Final drug target candidates obtained by this
system framework are presented along with implications of this
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Project description:Nosocomial outbreaks of infections caused by multidrug-resistant Acinetobacter baumannii have emerged as a serious threat to human health. The phosphoproteomics of pathogenic bacteria have been investigated for their role in virulence regulation networks. In this study, we analyzed the phosphoproteomics of two clinical isolates of A. baumannii: imipenem-sensitive strain SK17-S and -resistant strain SK17-R.
Project description:Total RNA isolated from mid-log-grown cultures of A. baumannii and mutant strain in three independent times. Expression profile of A. baumannii and its protein kinase muatant was compared. Overall design: Agilent one-color experiment, Organism: Acinetobacter baumannii, Agilent Custom Acinetobacter baumannii 8x15k Microarray designed by Genotypic Technology Private Limited (AMADID: 079361).
Project description:Total RNA isolated from mid-log-grown cultures of A. baumannii and mutant strain in three independent times. Expression profile of A. baumannii and its byk mutant was compared. Overall design: Agilent one-color experiment, Organism: Acinetobacter baumannii, Agilent Custom Acinetobacter baumannii 8x15k Microarray designed by Genotypic Technology Private Limited (AMADID: 079361).
Project description:RNA sequencing was carried out by ARK genomics, Edinburgh on an Illumina HiSeq platform to compare gene expression in Acinetobacter baumannii strain AYE and an adeRS deletion mutant in this strain.
Project description:RNA sequencing was carried out at BGI, Hong Kong on an Illumina HiSeq platform to compare gene expression in Acinetobacter baumannii strain S1 and an adeAB deletion mutant in this strain.
Project description:RNA sequencing was carried out at the University of Birmingham on an Illumina MiSeq platform to compare gene expression in Acinetobacter baumannii strain AYE and an adeB deletion mutant in this strain.
Project description:Acinetobacter baumannii AB042, a triclosan-resistant mutant, was examined for modulated gene expression using whole genome sequencing, transcriptomics, and proteomics in order to understand the mechanism of triclosan-resistance as well as its impact on A. Baumannii. Overall design: A triclosan mutant (AB042) was isolated by culturing A. baumannii ATCC 17978 in increasing concentrations of triclosan.