Year: 2026
Type: preprint
Abstract: Buruli ulcer (BU) is a neglected tropical skin disease caused by infection with Mycobacterium ulcerans . The mode of its transmission into the skin has not been fully clarified, but it is believed to involve mechanical transfer, perhaps by insect bites. M. ulcerans secretes a toxin called mycolactone which causes necrosis of the skin and formation of large skin lesions. Understanding the development of these skin lesions over time is crucial to understand the pathogenesis of BU. We formulate a mathematical model to describe the space-time dynamics of M. ulcerans bacteria, mycolactone and skin cell densities as well as fibrin deposition. We investigate the relative contributions to ulcer formation of direct cytotoxicity of mycolactone and ischaemia following the loss of coagulation control. Our results are consistent with existing biological evidence that higher mycolactone concentrations accelerate cell death. Furthermore, the model indicates that the rate of wound expansion is primarily controlled by the diffusion and net birth rate of bacteria, which sets the overall scaling for the speed of wound expansion, along with two dimensionless constants that define the shape of the trajectory of wound edge position against time, namely the ratio of the mycolactone diffusion coefficient to the bacterial diffusion coefficient, and the ratio of the mycolactone degradation rate to the bacterial net birth rate. When mycolactone diffuses significantly faster than bacteria spread or when mycolactone degrades more slowly than bacteria reproduce, the initial development of the wound is faster. In contrast, the long-term wound expansion speed appears to be relatively unchanged across a wide range of the dimensionless parameters. Author summary Buruli ulcer is a neglected tropical skin disease caused by Mycobacterium ulcerans , a bacterium that produces a toxin called mycolactone. The disease can cause extensive skin lesions, but the processes controlling how these lesions develop and expand are not fully understood. We developed a mathematical model to investigate how bacteria and mycolactone spread through the skin and contribute to skin-cell death. The model considers two possible mechanisms of tissue damage: direct toxic effects of mycolactone on skin cells and indirect damage caused by loss of blood supply following effects on endothelial cells. Our results show how differences in the sensitivity of skin-cell types to mycolactone can influence lesion development and suggest that indirect damage through ischaemia may contribute to tissue death even when mycolactone concentrations are too low to directly kill some cells. We also find that faster mycolactone diffusion or slower degradation can accelerate the initial development of a wound, while having relatively little effect on its longer-term expansion rate.
Institutions: University of Southampton, University of Surrey
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: University of Southampton
OpenAlex ID: W7221069714