ABSTRACT: Personalised genomic investigation reveals strain heterogeneity during chronic infection with E. coli ST131: The complete genome of E. coli ST131 Str. U12A
Project description:Personalised genomic investigation reveals strain heterogeneity during chronic infection with E. coli ST131: The complete genome of E. coli ST131 Str. U13A
Project description:Personalised genomic investigation reveals strain heterogeneity during chronic infection with E. coli ST131: The complete genome of E. coli ST131 Str. U14A
Project description:Personalised genomic investigation reveals strain heterogeneity during chronic infection with E. coli ST131: The complete genome of E. coli ST131 Str. U15A
Project description:Personalised genomic investigation reveals strain heterogeneity during chronic infection with E. coli ST131: Raw Ilumina sequence read data
Project description:Investigation of phenotypical changes between exhausted HCV-specific CD8+ T cells during chronic infection and after DAA-mediated cure investigation of heterogeneity withhin the HCV-specific CD8+ T cell population
Project description:Investigation of phenotypical changes between exhausted HCV-specific CD8+ T cells during chronic infection and after DAA-mediated cure investigation of heterogeneity withhin the HCV-specific CD8+ T cell population
Project description:Proteome analysis of ony commensal E. coli strain (ST10) and two pathogenic E. coli strains (from ST131) grown with and without sorbose
Project description:Six isolates of PT21/28 and six of PT32 were analysed by CGH using UBECarray3 microarrays (containing probes for E. coli K-12 str. MG1655 and O157:H7 str. EDL933 and Sakai) to define genotypic differences between phage types. gDNA from E.coli O157 str. Sakai was hybridised to all arrays to provide a universal control channel on all arrays.
Project description:Background: It remains unclear how high-risk Escherichia coli lineages, like sequence type (ST) 131, initially adapt to carbapenem exposure in its progression to becoming carbapenem resistant. Methods: Carbapenem mutation frequency was measured in multiple subclades of extended-spectrum β-lactamase (ESBL) positive ST131 clinical isolates using a fluctuation assay followed by whole genome sequencing (WGS) characterization. Genomic, transcriptomic, and porin analyses of ST131 C2/H30Rx isolate, MB1860, under prolonged, increasing carbapenem exposure was performed using two distinct experimental evolutionary platforms to measure fast vs. slow adaptation. Results: All thirteen ESBL positive ST131 strains selected from a diverse (n=184) ST131 bacteremia cohort had detectable ertapenem (ETP) mutational frequencies with a statistically positive correlation between initial ESBL gene copy number and mutation frequency (r = 0.87, P<1e-5). WGS analysis of mutants showed initial response to ETP exposure resulted in significant increases in ESBL gene copy numbers or mutations in outer membrane porin (Omp) encoding genes in the absence of ESBL gene amplification with subclade specific adaptations. In both experimental evolutionary platforms, MB1860 responded to initial ETP exposure by increasing blaCTX-M-15 copy numbers via modular, insertion sequence 26 (IS26) mediated pseudocompound transposons (PCTns). Transposase activity driven by PCTn upregulation was a conserved expression signal in both experimental evolutionary platforms. Stable mutations in Omp encoding genes were detected only after prolonged increasing carbapenem exposure consistent with clinical observations. Conclusions: ESBL gene amplification is a conserved response to initial carbapenem exposure, especially within the high-risk ST131 C2 subclade. Targeting such amplification could assist with mitigating carbapenem resistance development.
Project description:The aim of this study was to identify genes that can be targeted by helper drugs to counteract resistance towards ciprofloxacin (CIP). In order to reveal the impact of ciprofloxacin on the transcriptome, differential gene-expression analysis by RNA-seq was performed on the multidrug resistant E. coli strain ST131, treated with a clinically relevant concentration of ciprofloxacin (2 µg/mL).