GSE157956
RNA-seq strategy to study Mycobacterium ulcerans adaptation within our original mouse model of spontaneous healing.
Mycobacterium ulcerans is the causal agent of Buruli ulcer, a chronic infectious disease and the third most common mycobacterial disease worldwide. Without early treatment, M. ulcerans provokes massive skin ulcers, caused by the mycolactone toxin, its main virulence factor. However, spontaneous healing may occur in Buruli ulcer patients several months or years after the disease onset. We have shown, in an original mouse model, that bacterial load remains high and viable in spontaneously healed tissues, suggesting that M. ulcerans switches to low levels of mycolactone production, adapting its strategy to survive in such a hostile environment. We investigated the regulation of mycolactone production, by using an RNA-seq strategy to study bacterial adaptation within our original mouse model of spontaneous healing. Pathway analysis and characterization of the tissue environment showed that the bacillus adapted to its new environment by modifying its metabolic activity and switching nutrient sources. Thus, M. ulcerans ensures its survival in healing tissues by reducing its secondary metabolism, leading to an inhibition of mycolactone synthesis and changes in cell wall composition. These findings shed new light on mycolactone regulation and pave the way for new therapeutic strategies. Overall design: We used an optimized method, based on differential lysis, for the analysis of the whole transcriptome of Mycobacterium ulcerans. RNA was extracted from infected tail skin at the edema stage (30 days post-infection) and at the healing stage (60-75 days post-infection). We performed a comparative transcriptomic analysis of M. ulcerans using RNA-sequencing method.