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Subtractive Hybridization Reveals a Type I Polyketide Synthase Locus Specific to Mycobacterium ulcerans

Bacterial Pathogenesis Research Group, Department of Microbiology, Monash University, Clayton,¹ Department of Infectious Diseases, Austin and Repatriation Medical Centre, Heidelberg, Victoria, Australia,³ Unité Génétique Moléculaire Bactérienne, Institut Pasteur, Paris, France²

Received 12 May 2003/ Accepted 2 September 2003

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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