000151231 001__ 151231
000151231 005__ 20181203021958.0
000151231 022__ $$a0021-9193
000151231 02470 $$2PMID$$a15716437
000151231 0247_ $$2doi$$a10.1128/JB.187.5.1668-1676.2005
000151231 037__ $$aARTICLE
000151231 245__ $$aCommon evolutionary origin for the unstable virulence plasmid pMUM found in geographically diverse strains of Mycobacterium ulcerans
000151231 269__ $$a2005
000151231 260__ $$c2005
000151231 336__ $$aJournal Articles
000151231 520__ $$aThe 174-kb virulence plasmid pMUM001 in Mycobacterium ulcerans epidemic strain Agy99 harbors three very large and homologous genes that encode giant polyketide synthases (PKS) responsible for the synthesis of the lipid toxin mycolactone. Deeper investigation of M. ulcerans Agy99 resulted in identification of two types of spontaneous deletion variants of pMUM001 within a population of cells that also contained the intact plasmid. These variants arose from recombination between two 8-kb sections of the same plasmid sequence, resulting in the loss of a 65-kb region bearing two of the three mycolactone PKS genes. Investigation of nine diverse M. ulcerans strains by using PCR and Southern hybridization for eight pMUM001 gene sequences confirmed the presence of pMUM001-like elements (collectively called pMUM) in all M. ulcerans strains. Physical mapping of these plasmids revealed that like M. ulcerans Agy99, three strains had undergone major deletions in their mycolactone PKS loci. Online liquid chromatography-sequential mass spectrometry analysis of lipid extracts confirmed that strains with PKS deletions were unable to produce mycolactone or any related cometabolites. Interstrain comparisons of the plasmid gene sequences revealed greater than 98% nucleotide identity, and the phylogeny inferred from these sequences closely mimicked the phylogeny from a previous multilocus sequence typing study in which chromosomally encoded loci were used, a result that is consistent with the hypothesis that M. ulcerans diverged from the closely related organism Mycobacterium marinum by acquiring pMUM. Our results suggest that pMUM is a defining characteristic of M. ulcerans but that in the absence of purifying selection, deletion of plasmid sequences and a corresponding loss of mycolactone production readily arise.
000151231 700__ $$aStinear, Timothy P
000151231 700__ $$aHong, Hui
000151231 700__ $$aFrigui, Wafa
000151231 700__ $$aPryor, Melinda J
000151231 700__ $$aBrosch, Roland
000151231 700__ $$aGarnier, Thierry
000151231 700__ $$aLeadlay, Peter F
000151231 700__ $$0243892$$aCole, Stewart T$$g177247
000151231 773__ $$j187$$k5$$q1668-76$$tJournal of bacteriology
000151231 909C0 $$0252302$$pUPCOL$$xU11742
000151231 909CO $$ooai:infoscience.tind.io:151231$$pSV$$particle
000151231 937__ $$aEPFL-ARTICLE-151231
000151231 973__ $$aOTHER$$rREVIEWED$$sPUBLISHED
000151231 980__ $$aARTICLE