Mycobacterium ulcerans challenge strain selection for a Buruli ulcer controlled human infection model

PLoS Negl Trop Dis. 2024 May 3;18(5):e0011979. doi: 10.1371/journal.pntd.0011979. eCollection 2024 May.

Abstract

Critical scientific questions remain regarding infection with Mycobacterium ulcerans, the organism responsible for the neglected tropical disease, Buruli ulcer (BU). A controlled human infection model has the potential to accelerate our knowledge of the immunological correlates of disease, to test prophylactic interventions and novel therapeutics. Here we present microbiological evidence supporting M. ulcerans JKD8049 as a suitable human challenge strain. This non-genetically modified Australian isolate is susceptible to clinically relevant antibiotics, can be cultured in animal-free and surfactant-free media, can be enumerated for precise dosing, and has stable viability following cryopreservation. Infectious challenge of humans with JKD8049 is anticipated to imitate natural infection, as M. ulcerans JKD8049 is genetically stable following in vitro passage and produces the key virulence factor, mycolactone. Also reported are considerations for the manufacture, storage, and administration of M. ulcerans JKD8049 for controlled human infection.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Australia
  • Buruli Ulcer* / immunology
  • Buruli Ulcer* / microbiology
  • Humans
  • Mycobacterium ulcerans* / genetics

Grants and funding

SM is supported by a Postgraduate Scholarship from the National Health and Medical Research Council (NHMRC) of Australia (GNT1191368), JO is supported by an NHMRC EL1 Investigator grant (GNT2009548), TPS is supported by an NHMRC L2 Investigator grant (GNT1194325), JM is supported by an NHMRC L3 Investigator grant (GNT2016396), SJP is supported by NHMRC Ideas grant (GNT2021638). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.