Enrique Joffré

Enrique Joffré researches plasmid dynamics and the genomic epidemiology of multidrug-resistant E. coli. His work spans plasmid copy number control, within-host bacterial evolution, and One Health surveillance across clinical and environmental settings.

Researcher

Department of Medical Biochemistry and Microbiology at Uppsala University

enrique.joffre@imbim.uu.se

Research expertise and methodologies

I bridge the gap between bench-side experimentation and systems-level bioinformatics to characterize bacterial resistance and evolution.

  • Bacterial genetic manipulation: Expertise in strain engineering and directed mutagenesis.
  • Phenotypic characterization: Assessment of bacterial behavior, specifically focusing on virulence factors (adherence, motility, biofilm formation, genee and protein expression, and competition experiments) and antibiotic susceptibility/resistance profiles.
  • Experimental evolution: Designing and executing long-term evolution experiments to observe real-time adaptation.
  • Nanopore sequencing expertise: Comprehensive workflow management, from high-molecular-weight DNA extraction and library preparation (e.g., Ligation, Rapid, or Barcoding kits) to high-quality bacterial genomes by integrating short and long reads sequencing data.
  • Experimental Foundation: Expert in bacterial genetic manipulation, phenotypic characterization (virulence/biofilm), and Nanopore sequencing (end-to-end library prep to execution).
  • Genomic Architecture: Proficient in hybrid genome assembly, in-silico typing (ARGs/MLST/Replicons), epigenomic methylation analysis, and high-resolution phylogenomics (Bayesian/SNP-based/Pangenomics).
  • Systems Integration: Experienced in building reproducible, containerized pipelines (Nextflow) to integrate transcriptomic (DESeq2/GO/KEGG) and metabolomic data, enabling a holistic view of bacterial adaptation under environmental and clinical stressors.

Ongoing research projects

Within-Host evolution and diversity: I am investigating how E. coli evolves during infection. This includes a 5-year longitudinal study of KPC-producing E. coli in ICU patients and an analysis of within-host diversity in BSI and UTI patients. I use phenotypic screening to isolate distinct metabolic/AMR variants from monoclonal infections, followed by high-resolution genomics to map plasmid composition and adaptive mutation signatures.

AMR Transmission in Bolivia: I am mapping the spread of high-risk MDR E. coli (e.g., bla-NDM-5 ST167/ST405) across human (inpatient/outpatient UTI) and environmental (freshwater) interfaces in Bolivia. The goal is to characterize the genomic and plasmid-mediated drivers that allow these specific clonal groups to thrive under varying levels of anthropogenic pollution.

Mechanistic regulation of resistance and virulence:

  • We are testing the hypothesis that increased PCN under selective pressure elevates conjugative frequency. To validate this, we developed an HTS conjugation pipeline coupled with ddPCR.
  • Building on our discovery of AraC-like regulators in diarrheagenic E. coli, we are now defining the regulatory cross-talk in UPEC. I have identified novel negative regulators that coordinate virulence factor expression and antibiotic resistance pathways.

Key Publications

  1. Wang, H., Joffré, E. Plasmid copy number as a modulator in bacterial pathogenesis and antibiotic resistance. npj Antimicrob Resist 3, 72 (2025). https://doi.org/10.1038/s44259-025-00145-9
  2. Calderon Toledo C, von Mentzer A, Agramont J, Thorell K, Zhou Y, Szabó M, Colque P, Kuhn I, Gutiérrez-Cortez S, Joffré E. Circulation of enterotoxigenic Escherichia coli (ETEC) isolates expressing CS23 from the environment to clinical settings. mSystems. 2023 Oct 26;8(5):e0014123. https://doi.org/10.1128/msystems.00141-23
  3. Joffre E, Nicklasson M, Álvarez-Carretero S, Xiao X, Sun L, Nookaew I, Zhu B, Sjöling Å. The bile salt glycocholate induces global changes in gene and protein expression and activates virulence in enterotoxigenic Escherichia coli. Sci Rep. 2019 Jan 14;9(1):108. https://doi.org/10.1038/s41598-018-36414-z
  4. von Mentzer A, Connor TR, Wieler LH, Semmler T, Iguchi A, Thomson NR, Rasko DA, Joffre E, Corander J, Pickard D, Wiklund G, Svennerholm AM, Sjöling Å, Dougan G. Identification of enterotoxigenic Escherichia coli (ETEC) clades with long-term global distribution. Nat Genet. 2014 Dec;46(12):1321-6. https://doi.org/10.1038/ng.3145
  5. Paulshus E, Colque P, Kühn I, Tauhid T, Hu YOO, Zhou Y, Thorell K, Möllby R, Sørum H, Sjöling Å, Joffré E. Escherichia coli ST2797 Is Abundant in Wastewater and Might Be a Novel Emerging Extended-Spectrum Beta-Lactamase E. coli. Microbiol Spectr. 2023 Aug 17;11(4):e0448622. https://doi.org/10.1128/spectrum.04486-22
  6. Joffré E, Martín-Rodríguez AJ, Justh de Neczpal A, von Mentzer A, Sjöling Å. Emerging multi-drug resistant and extended-spectrum β-lactamase (ESBL)-positive enterotoxigenic E. coli (ETEC) clones circulating in aquatic environments and in patients. One Health. 2025 Jan 10;20:100968. https://doi.org/10.1016/j.onehlt.2025.100968

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