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: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:Phenotypic and Molecular Characterizations of Carbapenem-resistant Acinetobacter baumannii Isolates Collected within the EURECA Study
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:Acinetobacter baumannii is a Gram-negative pathogen that has emerged as one of the most troublesome pathogens for health care institutions globally. Bacterial quorum sensing (QS) is a process of cell-to-cell communication that relies on the production, secretion and detection of autoinducer (AI) signals to share information about cell density and regulate gene expression accordingly. The molecular and genetic basis of Acinetobacter baumannii virulence remains poorly understood. Therefore, the contribution of the abaI/abaR quorum sensing system to growth characteristics, morphology, biofilm formation, resistance, motility and virulence of Acinetobacter baumannii was studied in detail. RNA-seq analysis indicated that genes involved in various aspects of energy production and conversion, Valine, leucine and isoleucine degradation and lipid transport and metabolism are associated with bacterial pathogenicity. Our work provides a new insight into abaI/abaR quorum sensing system effects pathogenicity in A. baumannii. We propose that targeting the AHL synthase enzyme abaI could provide an effective strategy for attenuating virulence. On the contrary, interdicting the autoinducer synthase–receptor abaR elicits unpredictable consequences, which may lead to enhanced bacterial virulence.
