Helen Wang

Helen Wang researches how plasmid copy number control drives bacterial adaptation, virulence and antibiotic resistance. Her work spans molecular mechanisms of plasmid regulation across pathogens and plasmid-mediated resistance in polymicrobial biofilms on urinary catheters.

Associate Professor

Department of Medical Biochemistry and Microbiology at Uppsala University

helen.wang@imbim.uu.se

Helen's profile site

Helen's research group site

Research focus and interests

  • Infection Biology
  • host-pathogen interaction
  • Plasmid biology
  • Antibiotic resistance

Research expertise and methodologies

  • Bacterial pathogenesis
  • Molecular biology
  • Biochemistry
  • Clinical Bacteriology
  • infection model

Ongoing research projects

Our research focuses on antimicrobial resistance (AMR) by uncovering how plasmid copy number control drives bacterial adaptation, virulence, and antibiotic resistance. We study plasmids in clinically relevant pathogens, where dynamic increases in plasmid copy number rapidly boost resistance gene dosage, enabling transient survival during antibiotic treatment without stable genetic mutations. This reversible resistance state, often overlooked in clinical settings, likely contributes to treatment failure and infection relapse.

Using integrated genetic, biochemical, in vitro, in vivo, and clinical approaches, we define the molecular mechanisms that regulate plasmid copy number across diverse pathogens. We also investigate plasmid-mediated AMR within polymicrobial biofilms on urinary catheters, particularly interactions between Enterococcus and Escherichia coli that promote persistence and recurrence of infection. Our goal is to identify fundamental drivers of AMR and inform new strategies to improve antibiotic efficacy and patient outcomes.

Key Publications

  1. Wang H., Joffré E. (2025) Plasmid copy number as a modulator in bacterial pathogenesis and antibiotic resistance. npj Antimicrobials and Resistance, 3:72. https://doi.org/10.1038/s44259-025-00145-9
  2. Karlsson P., Zhang T., Järhult J.D., Joffré E., Wang H. (2025) Heterogeneity and metabolic diversity among Enterococcus species during long-term colonization. Microbiology Spectrum, e0316024. https://doi.org/10.1128/spectrum.03160-24
  3. Schubert K., Braly M., Zhang J., Muscolo M., Lam H., Hug K., Moore H., McCausland J.W., Terciano D., Lowe T., Lesser C.F., Jacobs-Wagner C., Wang H., Auerbuch V. (2025) The polyadenylase PAPI is required for virulence plasmid maintenance in pathogenic bacteria. PLoS Pathogens, 21(5):e1012655. https://doi.org/10.1371/journal.ppat.1012655
  4. Héchard T., Lu L., Edgren T., Celestine C., Wang H. (2025) YmoA functions as a molecular stress sensor in Yersinia. Communications Biology, 8. https://doi.org/10.1038/s42003-025-07675-y
  5. Nicoloff H., Hjort K., Andersson D.I., Wang H. (2024) Three concurrent mechanisms generate gene copy number variation and transient antibiotic heteroresistance. Nature Communications, 15(1):3981. https://doi.org/10.1038/s41467-024-48233-0
  6. Engling P., Héchard T., Edgren T., Francis M., Dersch P., Wang H. (2023) Calcium-responsive plasmid copy number regulation is dependent on discrete YopD domains in Yersinia pseudotuberculosis. Plasmid, 126:102683. https://doi.org/10.1016/j.plasmid.2023.102683
  7. Karlsson P., Pärssinen J., Danielsson E.A., Fatsis-Kavalopoulos N., Frithiof R., Hultström M., Lipcsey M., Järhult J.D., Wang H. (2023) Antibiotic use during coronavirus disease 2019 intensive care unit shape multidrug resistance bacteriuria: a Swedish longitudinal prospective study. Frontiers in Medicine, 10:1087446. https://doi.org/10.3389/fmed.2023.1087446
  8. Schneiders S., Héchard T., Edgren T., Avican K., Fällman M., Fahlgren A., Wang H. (2021) Spatiotemporal variations in growth rate and virulence plasmid copy number during Yersinia pseudotuberculosis infection. Infection and Immunity, 89(4). https://doi.org/10.1128/IAI.00710-20
  9. Wang H., Avican K., Fahlgren A., Erttmann S.F., Nuss A.M., Dersch P., Fällman M., Edgren T., Wolf-Watz H. (2016) Increased plasmid copy number is essential for Yersinia T3SS function and virulence. Science, 353(6298):492–495. https://doi.org/10.1126/science.aaf7501

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