A newly discovered mycobacterial pathogen isolated from laboratory colonies of Xenopus species with lethal infections produces a novel form of mycolactone, the Mycobacterium ulcerans macrolide toxin.
Mycobacterium ulcerans, the causative agent of Buruli ulcer, produces a macrolide toxin, mycolactone A/B, which is thought to play a major role in virulence. A disease similar to Buruli ulcer recently appeared in United States frog colonies following importation of the West African frog, Xenopus tropicalis. The taxonomic position of the frog pathogen has not been fully elucidated, but this organism, tentatively designated Mycobacterium liflandii, is closely related to M. ulcerans and Mycobacterium marinum, and as further evidence is gathered, it will most likely be considered a subspecies of one of these species. In this paper we show that M. liflandii produces a novel plasmid-encoded mycolactone, mycolactone E. M. liflandii contains all of the genes in the mycolactone cluster with the exception of that encoding CYP140A2, a putative p450 monooxygenase. Although the core lactone structure is conserved in mycolactone E, the fatty acid side chain differs from that of mycolactone A/B in the number of hydroxyl groups and double bonds. The cytopathic phenotype of mycolactone E is identical to that of mycolactone A/B, although it is less potent. To further characterize the relationship between M. liflandii and M. ulcerans, strains were analyzed for the presence of the RD1 region genes, esxA (ESAT-6) and esxB (CFP-10). The M. ulcerans genome strain has a deletion in RD1 and lacks these genes. The results of these studies show that M. liflandii contains both esxA and esxB.
Mve-Obiang
Armand
A
Department of Microbiology, 409 Walters Life Sciences, University of Tennessee, Knoxville, TN 37996-0845, USA.
Lee
Richard E
RE
Umstot
Edward S
ES
Trott
Kristin A
KA
Grammer
Timothy C
TC
Parker
John M
JM
Ranger
Brian S
BS
Grainger
Robert
R
Mahrous
Engu A
EA
Small
P L C
PL
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification*; D001483:Base Sequence; D018942:Macrolides; D051379:Mice; D008969:Molecular Sequence Data; D019911:Mycobacterium ulcerans / Q000472:pathogenicity*; D009170:Nontuberculous Mycobacteria / Q000472:pathogenicity*; D010446:Peptide Fragments / Q000235:genetics; D014774:Virulence; D014981:Xenopus / Q000382:microbiology*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; C489634:CFP-10 protein (71-85), Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D018942:Macrolides; D010446:Peptide Fragments; C117218:mycolactone