Experimental infection of ringtail possums with Mycobacterium ulcerans, the agent of Buruli ulcer

Abstract

Buruli ulcer (BU) is a necrotizing disease of skin and soft tissue caused by the bacterium Mycobacterium ulcerans (MU). In Australia, where the disease is spreading and case numbers increasing, native possum species act as reservoir hosts. To better understand the life history of MU in one of its natural hosts, we conducted intra-dermal challenge of six wild caught, MU-naïve common ringtail possums (Pseudocheirus peregrinus). All six animals developed BU disease consistent with that observed in naturally infected ringtail possums. Time to ulceration varied between 49 to 77 days (mean = 61.8 days). Molecular evidence of systemic infection was detected in five animals and was supported by consistent histopathological findings in four animals. Pathological findings included a random, multifocal, granulomatous hepatitis in four possums, one of which also had a mild, multifocal, interstitial granulomatous pneumonia. Acid-fast bacilli were only evident in inflammatory foci beyond the primary inoculation site in one possum. The ringtail possum model of MU infection is an important tool for the investigation of bacterial transmission dynamics, pathogenesis and immune response in a natural host. Data from this model may improve disease risk modelling and help identify intervention points to stop zoonotic transmission and disease spread.