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Infect. Immun. doi:10.1128/IAI.00970-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Globally distributed mycobacterial fish pathogens produce a novel plasmid-encoded toxic macrolide, mycolactone F

Department of Microbiology, University of Tennessee, Knoxville, Tennessee 37996-0845, USA; Department of Pharmaceutical Sciences, University of Tennessee Medical Health Center, Memphis, Tennessee 38163, USA; Israel Oceanographic and Limnological Research Ltd., National Center for Mariculture, Eilat 88112, Israel; Virginia Institute of Marine Science, College of William and Mary, Gloucester Point, VA 23062, USA

^* To whom correspondence should be addressed. Email: psmall{at}utk.edu.

	Abstract

Mycobacterium ulcerans and M. marinum are closely related pathogens which share an aquatic environment. The pathogenesis of these organisms in humans is limited by their inability to grow above 35°C. M. marinum causes systemic disease in fish but produces localized skin infections in humans. M. ulcerans causes Buruli ulcer, a severe human skin lesion. At the molecular level, M. ulcerans is distinguished from M. marinum by the presence of a virulence plasmid which encodes a macrolide toxin, mycolactone, as well as by hundreds of insertion sequences, particularly IS2404.

There has been a global increase in fish mycobacteriosis reports. An unusual clade of M. marinum has been reported from fish in the Red and Mediterranean Seas and a new mycobacterial species, M. pseudoshottsii, has been cultured from fish in the Chesapeake Bay, U.S.A. We have discovered that both groups of fish pathogens produce a unique mycolactone toxin, mycolactone F. Mycolactone F is the smallest mycolactone (m.w. 700) yet identified. The core lactone structure of mycolactone F is identical to that of M. ulcerans mycolactones, but a unique side chain structure is present. Mycolactone F produces apoptosis and necrosis on cultured cells, but is less potent than M. ulcerans mycolactones. Both groups of fish pathogens contain IS2404. In contrast to M. ulcerans and conventional M. marinum, mycolactone F-producing mycobacteria are incapable of growth above 30°C. This fact is likely to limit their virulence for humans. However, such isolates may provide a reservoir for horizontal transfer of the mycolactone plasmid in aquatic environments.

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