Buruli ulcer: Reductive evolution enhances pathogenicity of Mycobacterium ulcerans
Institut Pasteur, UP Pathogénomique Mycobactérienne Intégrée, Paris, France. Nature Reviews Microbiology
(Impact Factor: 23.57).
02/2009; 7(1):50-60. DOI: 10.1038/nrmicro2077
Buruli ulcer is an emerging human disease caused by infection with a slow-growing pathogen, Mycobacterium ulcerans, that produces mycolactone, a cytotoxin with immunomodulatory properties. The disease is associated with wetlands in certain tropical countries, and evidence for a role of insects in transmission of this pathogen is growing. Comparative genomic analysis has revealed that M. ulcerans arose from Mycobacterium marinum, a ubiquitous fast-growing aquatic species, by horizontal transfer of a virulence plasmid that carries a cluster of genes for mycolactone production, followed by reductive evolution. Here, the ecology, microbiology, evolutionary genomics and immunopathology of Buruli ulcer are reviewed.
Available from: academicjournals.org
- "The cutaneous mycobacteriosis is mostly seen in tropical and subtropical countries (Anne-Caroline et al., 2013; Emmanuelle et al., 2007; Hong et al., 2005; Laurence et al., 2009; Mac et al., 1948). The pathogenicity of MU is known to be linked to the secretion of a toxin named mycolactone (Caroline et al., 2009; Emmanuelle et al., 2007; Kathleen et al., 1999; Sarojini et al., 2005; Yoshito, 2011). The forms of Mycolactone are classified according to the origin of the productive strains. "
Available from: Dorothy kyerewah Yeboah-Manu
- "Examination of the classes of genes lost and modified in the M. ulcerans MRCA suggests a bacterial population occupying a niche environment that is aerobic, osmotically stable, dark (at least for lineage 3 isolates as shown by loss of UV-protecting pigment genes in a previous study) and possibly extracellular given the number of genes known to be involved in intracellular survival lost from M. ulcerans[1,13,21]. Support for an extracellular niche is also found in two separate studies showing M. ulcerans elaborates a mycolactone-rich extracellular matrix and specifically expresses a surface protein that promotes adherence during initial stages of biofilm formation [42,62]. "
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ABSTRACT: Mycobacterium ulcerans is an unusual bacterial pathogen with elusive origins. While closely related to the aquatic dwelling M. marinum, M. ulcerans has evolved the ability to produce the immunosuppressive polyketide toxin mycolactone and cause the neglected tropical disease Buruli ulcer. Other mycolactone-producing mycobacteria (MPM) have been identified in fish and frogs and given distinct species designations (M. pseudoshottsii, M. shinshuense, M. liflandii and M. marinum), however the evolution of M. ulcerans and its relationship to other MPM has not been defined. Here we report the comparative analysis of whole genome sequences from 30 MPM and five M. marinum.
A high-resolution phylogeny based on genome-wide single nucleotide polymorphisms (SNPs) showed that M. ulcerans and all other MPM represent a single clonal group that evolved from a common M. marinum progenitor. The emergence of the MPM was driven by the acquisition of the pMUM plasmid encoding genes for the biosynthesis of mycolactones. This change was accompanied by the loss of at least 185 genes, with a significant overrepresentation of genes associated with cell wall functions. Cell wall associated genes also showed evidence of substantial adaptive selection, suggesting cell wall remodeling has been critical for the survival of MPM. Fine-grain analysis of the MPM complex revealed at least three distinct lineages, one of which comprised a highly clonal group, responsible for Buruli ulcer in Africa and Australia. This indicates relatively recent transfer of M. ulcerans between these continents, which represent the vast majority of the global Buruli ulcer burden. Our data provide SNPs and gene sequences that can differentiate M. ulcerans lineages, suitable for use in the diagnosis and surveillance of Buruli ulcer.
M. ulcerans and all mycolactone-producing mycobacteria are specialized variants of a common Mycobacterium marinum progenitor that have adapted to live in restricted environments. Examination of genes lost or retained and now under selective pressure suggests these environments might be aerobic, and extracellular, where slow growth, production of an immune suppressor, cell wall remodeling, loss or modification of cell wall antigens, and biofilm-forming ability provide a survival advantage. These insights will guide our efforts to find the elusive reservoir(s) of M. ulcerans and to understand transmission of Buruli ulcer.
Available from: David Kateete
- "Tuberculosis (TB), the most important mycobacterial disease, is caused by genetically related species commonly referred to as "the Mycobacterium tuberculosis Complex" (MTC: Mycobacterium tuberculosis; M. bovis, also the causative agent of bovine TB; M. bovis BCG; M. africanum; M. carnetti and M. microti ). M. leprae and M. ulcerans are respectively the causative agents for two other important diseases, Leprosy and Buruli ulcer [3,4]. Besides the three major diseases, M. avium subsp. "
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ABSTRACT: Rhomboids are ubiquitous proteins with diverse functions in all life kingdoms, and are emerging as important factors in the biology of some pathogenic apicomplexa and Providencia stuartii. Although prokaryotic genomes contain one rhomboid, actinobacteria can have two or more copies whose sequences have not been analyzed for the presence putative rhomboid catalytic signatures. We report detailed phylogenetic and genomic analyses devoted to prokaryotic rhomboids of an important genus, Mycobacterium.
Many mycobacterial genomes contained two phylogenetically distinct active rhomboids orthologous to Rv0110 (rhomboid protease 1) and Rv1337 (rhomboid protease 2) of Mycobacterium tuberculosis H37Rv, which were acquired independently. There was a genome-wide conservation and organization of the orthologs of Rv1337 arranged in proximity with glutamate racemase (mur1), while the orthologs of Rv0110 appeared evolutionary unstable and were lost in Mycobacterium leprae and the Mycobacterium avium complex. The orthologs of Rv0110 clustered with eukaryotic rhomboids and contained eukaryotic motifs, suggesting a possible common lineage. A novel nonsense mutation at the Trp73 codon split the rhomboid of Mycobacterium avium subsp. Paratuberculosis into two hypothetical proteins (MAP2425c and MAP2426c) that are identical to MAV_1554 of Mycobacterium avium. Mycobacterial rhomboids contain putative rhomboid catalytic signatures, with the protease active site stabilized by Phenylalanine. The topology and transmembrane helices of the Rv0110 orthologs were similar to those of eukaryotic secretase rhomboids, while those of Rv1337 orthologs were unique. Transcription assays indicated that both mycobacterial rhomboids are possibly expressed.
Mycobacterial rhomboids are active rhomboid proteases with different evolutionary history. The Rv0110 (rhomboid protease 1) orthologs represent prokaryotic rhomboids whose progenitor may be the ancestors of eukaryotic rhomboids. The Rv1337 (rhomboid protease 2) orthologs appear more stable and are conserved nearly in all mycobacteria, possibly alluding to their importance in mycobacteria. MAP2425c and MAP2426c provide the first evidence for a split homologous rhomboid, contrasting whole orthologs of genetically related species. Although valuable insights to the roles of rhomboids are provided, the data herein only lays a foundation for future investigations for the roles of rhomboids in mycobacteria.
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