Differential gene repertoire in Mycobacterium ulcerans identifies candidate genes for patho-adaptation.
BACKGROUND
Based on large genomic sequence polymorphisms, several haplotypes belonging to two major lineages of the human pathogen Mycobacterium ulcerans could be distinguished among patient isolates from various geographic origins. However, the biological relevance of insertional/deletional diversity is not understood.


METHODS
Using comparative genomics, we have investigated the genes located in regions of difference recently identified by DNA microarray based hybridisation analysis. The analysed regions of difference comprise approximately 7% of the entire M. ulcerans genome.


RESULTS
Several different mechanisms leading to loss of functional genes were identified, ranging from pseudogenization, caused by frame shift mutations or mobile genetic element interspersing, to large sequence polymorphisms. Four hot spot regions for genetic instability were unveiled. Altogether, 229 coding sequences were found to be differentially inactivated, constituting a repertoire of coding sequence variation in the rather monomorphic M. ulcerans.


CONCLUSIONS
The differential gene inactivation patterns associated with the M. ulcerans haplotypes identified candidate genes that may confer enhanced adaptation upon ablation of expression. A number of gene conversions confined to the classical lineage may contribute to particular virulence of this group comprising isolates from Africa and Australia. Identification of this spectrum of anti-virulence gene candidates expands our understanding of the pathogenicity and ecology of the emerging infectious disease Buruli ulcer.
Käser
Michael
M
Swiss Tropical Institute, Basel, Switzerland. m.kaeser@unibas.ch
Pluschke
Gerd
G
D000818:Animals; D001483:Base Sequence; D054312:Buruli Ulcer / Q000382:microbiology*; D017931:DNA Primers / Q000737:chemistry; D004269:DNA, Bacterial / Q000235:genetics / Q000302:isolation & purification; D005399:Fishes / Q000382:microbiology; D014644:Genetic Variation; D016680:Genome, Bacterial; D005843:Geography; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D019911:Mycobacterium ulcerans / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction
D017931:DNA Primers; D004269:DNA, Bacterial