Lack of insertional-deletional polymorphism in a collection of Mycobacterium ulcerans isolates from Ghanaian Buruli ulcer patients

Mycobacterium ulcerans causes the devastating infectious skin disease Buruli ulcer and has a monomorphic population structure. The resolution of conventional genetic fingerprinting methods is therefore not sufficient for micro-epidemiological studies aiming to characterize transmission pathways. In a previous comparative genomic hybridisation analysis with a microarray covering part of the M. ulcerans genome, we have found insertion sequence-associated extensive insertional-deletional sequence polymorphisms among M. ulcerans isolates of diverse geographic origin that allowed distinguishing between strains coming from different continents. Since large numbers of insertion sequences are spread over the genome of African M. ulcerans strains, we reasoned that these may drive large sequence polymorphism in otherwise clonal local mycobacterial populations. In this study, we used a printed DNA microarray covering the whole genome of the Ghanaian M. ulcerans reference strain Agy99 for comparative genomic hybridisation. The assay identified multiple regions of difference when DNA of a Japanese M. ulcerans strain was analyzed. In contrast, not a single insertional/deletional genomic variation was found within a panel of disease isolates coming from a Buruli ulcer endemic area of Ghana. These results indicate that - despite the expectations deduced from other mycobacterial pathogens - only analyses of single nucleotide polymorphisms will have the potential to differentiate local populations of M. ulcerans