Project description:Studies of expression of mechanims of defense of the Acinetobacter sp.5-2Ac.02 from airborne hospital environment under stress conditions, such as SOS response (ROS response, heavy metals resistant mechanisms, peptides), as well as Quorum network (acetoin cluster and aromatics biodegradation cluster). Characterization functional of AcoN-like as negative regulator protein from acetoin cluster in Acinetobacter spp. Strains
Project description:Unknown are the mechanisms of tolerance and persistence associated to several compounds in A.baumannii clinical isolates. Using transcriptomical and microbiological studies, we found a link between bacterial tolerance mechanisms to clorhexidine as well as the development of persistence in presence of imipenem in an A.baumannii strain belonging to ST-2 clinical clone (carbapenem-resistant with OXA-24 ß-lactamase and AbkAB TA system by plasmid). Interestingly, in A.baumannii ATCC17978 strain (carbapenem-susceptible isolate which carries AbkAB TA system by plasmid) showed persistence in presence of imipenem.
Project description:Purpose: The goal of this study was to elucidate the collateral effects associated with OXA-23 overexpression on the Acinetobacter baumannii global transcriptome. Results: Besides the 99.73-fold increase in blaOXA-23 transcript upon IPTG induction, no other transcripts showed more than a 2-fold change compared to the wildtype control. This suggests that OXA-23 over expression to levels similarly observed in multi drug resistant A. baumannii clinical isolates does not effect the transcriptome.
Project description:Cefiderocol (CFDC) is a novel chlorocatechol-substituted siderophore approved to treat complicated urinary tract infections and for hospital-acquired and ventilator-acquired pneumonia. In previous work, human fluids, were shown to increase the minimum inhibitory concentration (MICs) of Acinetobacter baumannii against CFDC and reduce the expression of genes related to iron uptake systems, which could explain the need for higher concentrations of CFDC to exert inhibitory action. Herein, we analyzed the impact of human urine (HU), which contains low albumin concentrations, on the expression of iron-uptake related genes and MIC values of two carbapenem-resistant A. baumannii. Levels of resistance to CFDC were not modified by HU in strain AMA40 but were reduced in the case of strain AB5075. Testing other carbapenem-resistant A. baumannii isolates showed that the CFDC MICs were unmodified or reduced in the presence of HU. The expression of piuA, pirA, bauA, and bfnH determined by qRT-PCR was enhanced in both strains when HU was present in the culture medium. All four tested genes are involved in recognizing ferric siderophore complexes or internalization into the cell’s cytosol. In contrast, the effect of HU on genes associated with resistance to β-lactams, antibiotics commonly used to treat urinary tract infections caused by A. baumannii, was variable; the transcriptional analysis of pbp1, pbp3, blaOXA-51-like, blaADC, and blaNDM-1 showed significant variation. In summary, HU, probably due to the albumin and free iron content, does not adversely impact or slightly improves the activity of CFDC when tested against A. baumannii in urine in contrast to other human bodily fluids.
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:Colistin is a crucial last-line drug used for the treatment of life-threatening infections caused by multi-drug resistant strains of the Gram-negative bacteria, Acinetobacter baumannii. However, colistin resistant A. baumannii isolates can be isolated following failed colistin therapy. Resistance is most often mediated by the addition of phosphoethanolamine (pEtN) to lipid A by PmrC, following missense mutations in the pmrCAB operon encoding PmrC and the two-component signal transduction system PmrA/PmrB. We recovered an isogenic pair of A. baumannii isolates from a single patient before (6009-1) and after (6009-2) failed colistin treatment that displayed low/intermediate and high levels of colistin resistance, respectively. To understand how increased colistin-resistance arose, we genome sequenced each isolate which revealed that 6009-2 had an extra copy of the insertion sequence element ISAba125 within a gene encoding an H-NS-family transcriptional regulator. Consequently, transcriptomic analysis of the clinical isolates identified was performed and more than 150 genes as differentially expressed in the colistin-resistant, hns mutant, 6009-2. Importantly, the expression of eptA, encoding a second lipid A-specific pEtN transferase, but not pmrC, was significantly increased in the hns mutant. This is the first time an H-NS-family transcriptional regulator has been associated with a pEtN transferase and colistin resistance.
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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