ESR15 small

NOVEL CONCEPTS IN SUPPORT OF CLINICAL MANAGEMENT OF AMR

Comparative genomics and transcriptional profiles of multi-drug resistant Enterobacteriaceae and Acinetobacters

The project aims to better understand antimicrobial resistance mechanisms through genomic and transcriptomic studies. The ultimate goal is to design new molecular and phenotypic tests for rapid and accurate detection of emerging mechanisms of resistance to “old” revisited drugs such as colistin.

Aim #1

  • Assessment of adaptive changes in presence or absence of various molecules such as selected drugs, new anti-microbial compounds and anti-biofilm compounds
  • Comparison at the genome level: identification of SNP, mobile elements, genes involved in the changes
  • Identification of metabolic pathways potentially involved through transcriptome analyses and possibly metabolomics
  • Detection of adaptive changes by phenotypic methods: testing of new substrates, modification of existing culture media…

Aim #2

  • Design of new diagnostic tests for AMR detection:
  • Molecular-based tests (multiplex PCR, Argene tests…) for rapid and accurate detection of new plasmid- or chromosome-mediated AMR
  • New phenotypic-based tests

Bacterial isolates

  • Species of interest: at least Escherichia coli, Klebsiella spp
  • Origin of isolates: samples from human, environmental , food and animal sources
  • Access to isolates: bioMérieux strain collection, European network through the team at University of Antwerp, FDA-CDC Antimicrobial Resistance Isolate Bank
  • Initial focus on mcr-1 gene that confers a plasmid-mediated resistance to colistin frequently used as one of last-resort antibiotics

Main tasks

  • Create curated genome database including plasmid content
  • Perform genome sequencing, RNAseq experiments, phenotypic antibiotic susceptibility testing of representative strains,
  • Design and validate a streamlined and user-friendly sequencing bioinformatic pipeline,
  • Perform transcriptomic studies in absence / presence of relevant antibiotics or other compounds in different concentrations and combinations
  • Identify / describe / confirm genes associated to resistance for the design of new molecular AMR tests.

Deliverables

  • Assembly of relevant panels of strains through internal and external sourcing
  • Easy-to-use bioinformatics interfaces for genomic and transcriptomic analyses by microbiologists
  • User-friendly set of bioinformatics tools to rapidly access, visualize and combine information from genomic and phenotypic sources into a unique platform and conduct relevant  analyses
  • Proof-of-concept on new phenotypic and molecular AMR diagnosis tests
  • Performance evaluation of new AMR tests in clinical microbiology laboratory settings
  • Publications
  • bioMérieux
    Innovation Unit – Biology Research Department
    38390 La Balme Les Grottes
    France
  • Oxford University Hospitals
    John Radcliffe Hospital
    Oxford
    England

Specific profile requirements

  • Master degree in Microbiology
  • Knowledge in bioinformatics
  • Willingness to perform microbiology lab work and bioinformatics analyses
  • Excellent interpersonal skills and ability to work with different units and departments within the organization