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: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. Overall design: mRNA profiles of two isolates taken from a single patient, one before and one after colistin treatment, cDNA libraries were sequenced on an Illumina HiSeq 2000
Project description:We analyzed the extracellular proteome of colistin-resistant Korean Acinetobacter baumannii (KAB) strains to identify proteome profiles that can be used to characterize extensively drug-resistant KAB strains.
Project description:To explore how multiple drug-resistant A. baumannii response to colistin resistance, we compared the genomic, transcriptional and proteomic profile of A. baumannii MDR-ZJ06 to that of induced colistin resistant strain ZJ06-200P5-1.
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: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.
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).