Mycobacterium ulceranschallenge strain selection for a Buruli ulcer controlled human infection model

Abstract

AbstractCritical scientific questions remain regarding infection withMycobacterium 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 supportingM. ulceransJKD8049 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, asM. ulceransJKD8049 is genetically stable followingin vitropassage and produces the key virulence factor, mycolactone. Also reported are considerations for the manufacture, storage, and administration ofM. ulceransJKD8049 for controlled human infection.