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Background    Mycobacterium ulcerans  is the causative agent of Buruli ulcer (BU), a destructive skin disease found predominantly in sub-Saharan Africa and south-eastern Australia. The precise mode(s) of transmission and environmental reservoir(s) remain unknown, but several studies have explored the role of aquatic invertebrate species. The purpose of this study was to investigate the environmental distribution of  M. ulcerans  in south-eastern Australia.    Methodology/Principal Findings  A range of environmental samples was collected from Point Lonsdale (a small coastal town southwest of Melbourne, Australia, endemic for BU) and from areas with fewer or no reported incident cases of BU.  Mycobacterium ulcerans  DNA was detected at low levels by real-time PCR in soil, sediment, water residue, aquatic plant biofilm and terrestrial vegetation collected in Point Lonsdale. Higher levels of  M. ulcerans  DNA were detected in the faeces of common ringtail ( Pseudocheirus peregrinus ) and common brushtail ( Trichosurus vulpecula ) possums. Systematic testing of possum faeces revealed that  M. ulcerans  DNA could be detected in 41% of faecal samples collected in Point Lonsdale compared with less than 1% of faecal samples collected from non-endemic areas (p<0.0001). Capture and clinical examination of live possums in Point Lonsdale validated the accuracy of the predictive value of the faecal surveys by revealing that 38% of ringtail possums and 24% of brushtail possums had laboratory-confirmed  M. ulcerans  skin lesions and/or  M. ulcerans  PCR positive faeces. Whole genome sequencing revealed an extremely close genetic relationship between human and possum  M. ulcerans  isolates.    Conclusions/Significance  The prevailing wisdom is that  M. ulcerans  is an aquatic pathogen and that BU is acquired by contact with certain aquatic environments (swamps, slow-flowing water). Now, after 70 years of research, we propose a transmission model for BU in which terrestrial mammals are implicated as reservoirs for  M. ulcerans .

A Major Role for Mammals in the Ecology of Mycobacterium ulcerans