Abstract
Buruli ulcer is a neglected tropical infectious disease, produced by the environmentally persistent pathogen Mycobacterium ulcerans (MU). Neither the ecological niche nor the exact mode of transmission of MU are completely elucidated. However, some environmental factors, such as the concentration in chitin and pH values, were reported to promote MU growth in vitro. We pursued this research using next generation sequencing (NGS) and mRNA sequencing to investigate potential changes in MU genomic expression profiles across in vitro environmental conditions known to be suitable for MU growth. Supplementing the growth culture medium in either chitin alone, calcium alone, or in both chitin and calcium significantly impacted the MU transcriptome and thus several metabolic pathways, such as, for instance, those involved in DNA synthesis or cell wall production. By contrast, some genes carried by the virulence plasmid and necessary for the production of the mycolactone toxin were expressed neither in control nor in any modified environments. We hypothesized that these genes are only expressed in stressful conditions. Our results describe important environmental determinants playing a role in the pathogenicity of MU, helping the understanding of its complex natural life cycle and encouraging further research using genomic approaches.
Highlights
Mycobacterium ulcerans is the etiological agent of Buruli ulcer (BU), a neglected infectious disease characterized by skin ulcers which, in the absence of early treatments, produce a wide tissue destruction, leading to disfigurement and disability [1]
The high variations in the estimates of M. ulcerans (MU) cells across replicates presently observed at date t = 33 days post-inoculation are not surprising; similar results were observed at individual dates even if MU growth kinetics significantly differed among culture conditions when taking several dates into consideration [16]
Our data suggest that the PCR-based detection of the pMUM001 virulence plasmid does not necessarily translate into MU infection risks to humans
Summary
Mycobacterium ulcerans is the etiological agent of Buruli ulcer (BU), a neglected infectious disease characterized by skin ulcers which, in the absence of early treatments, produce a wide tissue destruction, leading to disfigurement and disability [1]. In the number of human cases, BU is the third mycobacteriosis after tuberculosis and leprosy in the world showing a drastic increase in the number of reported cases in the last ten years. This is especially true in Western Africa, where the Republic of. M. ulcerans (MU) has been described as an environmentally persistent mycobacterium evolved from the more generalist Mycobacterium marinum [4,5]. Some of the characteristics of this evolution include proliferation of insertion sequences (IS2404 and IS2604), genome reduction, pseudogene formation and the horizontal transfer of the virulence plasmid pMUM001 that encodes the genes involved in the production of mycolactone, the lipid toxin responsible, in part, for BU ulcers in humans
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