Transcriptome Analysis of Animal Models of Spontaneous Healing of Buruli Ulcer

Buruli ulcer (BU) is a neglected emerging infectious disease caused by Mycobacterium ulcerans. BU has become the third most prevalent mycobacteriosis worldwide, after tuberculosis and leprosy. Limited knowledge of the disease and the fact that it affects mainly poor rural communities contribute to underreporting of cases. Nevertheless, there are 6000 reported cases every year, of which more than 50% are children under the age of 15. For these reasons, the World Health Organization (WHO) has recognized BU as an emerging infectious disease with an important public health impact; that is both devastating for the individual and catastrophic for the economy of affected households.

M. ulcerans produces a dermonecrotic toxin, mycolactone, which induces extensive destruction of the skin and soft tissues with the formation of large ulcers, as well as bone and joint lesions. No specific vaccine is currently available for BU and because the disease progresses without pain or fever, treatment is frequently sought too late and often requires high cost extensive surgery at major hospitals. Therefore, it is not surprising that 25% of those infected - in particular children - become permanently disabled and endure severe social and economic problems. However, in a recent epidemiological study, our consortium found that 5% of BU patients display spontaneous healing without resorting to treatment.

The hypothesis underlying this project is that resistant vs. susceptible host responses to M. ulcerans infection are a result of differences at the level of gene expression, which can be tested by exploring two animal models of resistance recently developed by our consortium.

Therefore, this project has two main goals: (1) elucidate what constitutes a protective response against M. ulcerans infection and (2) understand the cross-talk between the host and the pathogen during the infectious process in resistant vs. susceptible hosts.

The understanding of the spontaneous healing process of BU lesions requires a global approach integrating different facets of the infectious process. By combining forefront technologies and unexplored animal models of resistance to M. ulcerans infection, this project provides a unique opportunity to identify critical pathways involved in the control of BU, from both the host and pathogen perspective. The multidisciplinary approach of this project relies on the complementary expertise of the teams involved to achieve integration of basic science and enabling state-of-the-art technologies. The CNAG will contribute to the success of this project with its expertise in applied genomics and high-throughput sequencing, specifically RNA Sequencing (RNA-Seq).

BU_SPONT_HEAL is funded by the 2015 call “Infect-ERA” an ERA-NET on human infectious diseases funded under the Seventh Research Framework Programme (2013 – 2016).

Jorge Pedrosa