Project description:Kim2009 - Genome-scale metabolic network of
Acinetobacter baumannii (AbyMBEL891)
This model is described in the article:
Genome-scale metabolic
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):
339-348
Abstract:
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
approach.
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Project description:A major reservoir for spread of the emerging pathogen Acinetobacter baumannii is hopsital surfaces, where bacteria persist in a desiccated state. To identify gene products influencing desiccation survival, a transposon sequencing (Tn-seq) screen was performed. Using this approach, we identified genes both positively and negatively impacting the desiccation tolerance of A. baumannii.
Project description:In recent years, the Gram-negative bacterium Acinetobacter baumannii has garnered considerable attention for its unprecedented capacity to rapidly develop resistance to antibacterial therapeutics. This is coupled with the seemingly epidemic emergence of new hyper-virulent strains. Although strain-specific differences for A. baumannii isolates have been well described, these studies have primarily focused on proteinaceous factors. At present, only limited publications have investigated the presence and role of small regulatory RNA (sRNA) transcripts. Herein, we perform such an analysis, describing the RNA-seq-based identification of 78 A. baumannii sRNAs in the AB5075 background. Together with six previously identified elements, we include each of these in a new genome annotation file, which will serve as a tool to investigate regulatory events in this organism. Our work reveals that the sRNAs display high expression, accounting for >50 % of the 20 most strongly expressed genes. Through conservation analysis we identified six classes of similar sRNAs, with one found to be particularly abundant and homologous to regulatory, C4 antisense RNAs found in bacteriophages. These elements appear to be processed from larger transcripts in an analogous manner to the phage C4 molecule and are putatively controlled by two further sRNAs that are strongly antisense to them. Collectively, this study offers a detailed view of the sRNA content of A. baumannii, exposing sequence and structural conservation amongst these elements, and provides novel insight into the potential evolution, and role, of these understudied regulatory molecules. This study is based on the annotation of novel sRNAs on basis of an Acinetobacter baumannii RNA sequencing dataset. Each sample was generated by pooling three independent biological replicate RNA preps
Project description:We performed RNAseq for gene expression analysis for six strains of Acinetobacter Baumannii isolated from blood samples (defined as strains 1, 2, 3, 4 and 6) of patients hospitalized at the University Hospital \\"San Giovanni di Dio e Ruggi d'Aragona\\" (Salerno, Italy)