01646nas a2200313 4500000000100000008004100001260001300042653002400055653002100079653002300100653001600123653001100139653001500150653002800165653002600193653001800219653003100237653003000268653002300298100001400321700001500335700001700350700001300367245010900380300001200489490000800501520080900509022001401318 2003 d c2003 Dec10aAmino Acid Sequence10aBacterial Toxins10aBlotting, Southern10aEpothilones10aHumans10aMacrolides10aMolecular Sequence Data10aMultienzyme Complexes10aMycobacterium10aNucleic Acid Hybridization10apolymerase chain reaction10aSequence Alignment1 aJenkin GA1 aStinear TP1 aJohnson PD R1 aDavies J00aSubtractive hybridization reveals a type I polyketide synthase locus specific to Mycobacterium ulcerans. a6870-820 v1853 a

Mycobacterium ulcerans causes Buruli ulcer, the third most prevalent mycobacterial infection of immunocompetent humans after tuberculosis and leprosy. Recent work has shown that the production by M. ulcerans of mycolactone, a novel polyketide, may partly explain the pathogenesis of Buruli ulcer. To search for the genetic basis of virulence in M. ulcerans, we took advantage of the close genetic relationship between M. ulcerans and Mycobacterium marinum by performing genomic suppressive subtractive hybridization of M. ulcerans with M. marinum. We identified several DNA fragments specific to M. ulcerans, in particular, a type I polyketide synthase locus with a highly repetitive modular arrangement. We postulate that this locus is responsible for the synthesis of mycolactone in M. ulcerans.

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