Hervé Nicoloff

Bacteria don't always need a new gene to resist an antibiotic. They can take one that already exists and copy it, repeatedly and temporarily. Hervé Nicoloff works on how that happens and what it means for treatment.

Associate Professor

Department of Medical Biochemistry and Microbiology at Uppsala University

herve.nicoloff@imbim.uu.se

Hervé's profile site

Research focus and interests

  • Antibiotic resistance
  • Antibiotic heteroresistance
  • Resistance mechanisms
  • Tandem genetic amplifications
  • Plasmids
  • Plasmids copy number regulation
  • Bacterial populations genetics
  • Bacterial fitness

Research expertise and methodologies

  • Long-read and short read sequencing
  • Optimization of long-read sequencing (Nanopore)
  • Bacterial molecular genetics
  • Targeted mutagenesis
  • Fitness determination
  • Microbiology

Ongoing research projects

Current projects:

  • Distribution of tandem genetic amplifications increasing the gene copy number of resistance genes in bacterial populations and its impact on heteroresistance
  • Plasmid copy number increase as a mechanism of antibiotic heteroresistance and its impact on horizontal gene transfer of resistance genes
  • Potential for β-lactamases to cause heteroresistance when present at increased copy number

(Hopefully) future projects:

  • Genome-wide characterization of bacterial genetic plasticity and its impact on the evolution of antibiotic heteroresistance
  • Expression and regulation of antibiotic resistance genes in clinical isolates: role of genetic context (promoters) and impact on observed discrepancies between genotypes and antimicrobial susceptibility tests

Key Publications

  1. Jonsson S., Guliaev A., Berryhill B.A., Andersson D.I., Nicoloff H. (2026) The dynamic distribution of genetic tandem amplifications in a heteroresistant Escherichia coli population revealed by ultra-deep long read sequencing. Nature Communications. https://doi.org/10.1038/s41467-026-70044-8
  2. Heyman G., Jonsson S., Fatsis-Kavalopoulos N., Hjort K., Nicoloff H., Furebring M., Andersson D.I. (2025) Prevalence, misclassification, and clinical consequences of the heteroresistant phenotype in Escherichia coli bloodstream infections in patients in Uppsala, Sweden: a retrospective cohort study. The Lancet Microbe, 6(4):101010. https://doi.org/10.1016/j.lanmic.2024.101010
  3. Nicoloff H., Hjort K., Wang H., Andersson D.I. (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
  4. Nicoloff H., Hjort K., Levin B.R., Andersson D.I. (2019) The high prevalence of antibiotic heteroresistance in pathogenic bacteria is mainly caused by gene amplification. Nature Microbiology, 4(3):504–514. https://doi.org/10.1038/s41564-018-0342-0
  5. Andersson D.I., Nicoloff H., Hjort K. (2019) Mechanisms and clinical relevance of bacterial heteroresistance. Nature Reviews Microbiology, 17(8):479–496. https://doi.org/10.1038/s41579-019-0218-1

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