Analysis of key genes in Mycobacterium ulcerans reveals conserved RNA structural motifs and regions with apparent pressure to remain unstructured

Abstract

Buruli Ulcer is a neglected tropical disease that results in disfiguring and dangerous lesions in affected persons across a wide geographic area, including much of West Africa. The causative agent of Buruli Ulcer is Mycobacterium ulcerans, a relative of the bacterium that causes tuberculosis and leprosy. Few therapeutic options exist for the treatment of this disease beyond antibiotics in the early stages, which are frequently ineffective, and surgical removal in the later stage. In this study we analyze six genes in Mycobacterium ulcerans that have high potential of therapeutic targeting. We focus our analysis on a combined in silico and comparative sequence study of potential RNA secondary structure across these genes. The result of this work was the comprehensive local RNA structural landscape across each of these significant genes. This revealed multiple sites of ordered and evolved RNA structure interspersed between sequences that either have no bias for structure or, indeed, appear to be ordered to be unstructured and (potentially) accessible. In addition to providing data that could be of interest to basic biology, our results provide guides for efforts aimed at targeting this pathogen at the RNA level. We explore this latter possibility through the in silico analysis of antisense oligonucleotides that could potentially be used to target pathogen RNA.