Microbiology 151 (2005), 683-692; DOI 10.1099/mic.0.27674-0
© 2005 Society for General Microbiology
Functional analysis and annotation of the virulence plasmid pMUM001 from Mycobacterium ulcerans
Timothy P. Stinear1,3,
Melinda J. Pryor2,
,
Jessica L. Porter3 and
Stewart T. Cole1
1 Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, 28 Rue du Docteur Roux, 75725 Paris Cedex 15, France
2 Plate-Forme 4 – Intégration et analyse génomiques, Génopole, Institut Pasteur, 28 Rue du Docteur Roux, 75725 Paris Cedex 15, France
3 Australian Bacterial Pathogenesis Program, Department of Microbiology, Monash University, Clayton, 3800, Australia
Correspondence
Timothy P. Stinear
tim.stinear{at}med.monash.edu.au
The presence of a 174 kb plasmid called pMUM001 in Mycobacterium ulcerans, the first example of a mycobacterial plasmid encoding a virulence determinant, was recently reported. Over half of pMUM001 is devoted to six genes, three of which encode giant polyketide synthases (PKS) that produce mycolactone, an unusual cytotoxic lipid produced by M. ulcerans. In this present study the remaining 75 non-PKS-associated protein-coding sequences (CDS) are analysed and it is shown that pMUM001 is a low-copy-number element with a functional ori that supports replication in Mycobacterium marinum but not in the fast-growing mycobacteria Mycobacterium smegmatis and Mycobacterium fortuitum. Sequence analyses revealed a highly mosaic plasmid gene structure that is reminiscent of other large plasmids. Insertion sequences (IS) and fragments of IS, some previously unreported, are interspersed among functional gene clusters, such as those genes involved in plasmid replication, the synthesis of mycolactone, and a potential phosphorelay signal transduction system. Among the IS present on pMUM001 were multiple copies of the high-copy-number M. ulcerans elements IS2404 and IS2606. No plasmid transfer systems were identified, suggesting that trans-acting factors are required for mobilization. The results presented here provide important insights into this unusual virulence plasmid from an emerging but neglected human pathogen.
Abbreviations: BU, Buruli ulcer; CDS, protein-coding sequence(s); EOT, efficiency of transformation; FHA, fork-head-associated; IS, insertion sequence(s); PKS, polyketide synthase(s)
The GenBank/EMBL/DDBJ accession number for the sequence of pMUM001 and its annotation reported in this paper is BX649209.
A summary of the 81 predicted CDS in Mycobacterium ulcerans pMUM001 is shown in Supplementary Table S1, available with the online version of this paper at http://mic.sgmjournals.org.
Present address: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia.
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Copyright © 2005 Society for General Microbiology.
