Comparative genomics shows Mycobacterium ulcerans migration and expansion has preceded the rise of Buruli ulcer in south-eastern Australia.

Since 2012, cases of the neglected tropical disease Buruli ulcer, caused by infection with Mycobacterium ulcerans, have increased 100-fold since 2000 around Melbourne, (population 4.4 million) the capital of Victoria in temperate south-eastern Australia. The reasons for this increase are unclear. Here, we have used whole genome sequence comparisons of 178 M. ulcerans isolates obtained primarily from human clinical specimens, spanning 70 years, to model the population dynamics of this pathogen from this region. Using phylogeographic and advanced Bayesian phylogenetic approaches, we found that there has been a migration of the pathogen from the east of the state, beginning in the 1980s, 300km west to the major human population centre around Melbourne. This move has then been followed by a significant increase in M. ulcerans population size. These analyses inform our thinking around Buruli ulcer transmission and control, indicating that M. ulcerans is introduced to a new environment and then expands, rather than the awakening of a quiescent pathogen reservoir.