Detection of Mycolactone A/B in Mycobacterium ulcerans-Infected Human Tissue.
BACKGROUND
Mycobacterium ulcerans disease (Buruli ulcer) is a neglected tropical disease common amongst children in rural West Africa. Animal experiments have shown that tissue destruction is caused by a toxin called mycolactone.


RESULTS
A molecule was identified among acetone-soluble lipid extracts from M. ulcerans (Mu)-infected human lesions with chemical and biological properties of mycolactone A/B. On thin layer chromatography this molecule had a retention factor value of 0.23, MS analyses showed it had an m/z of 765.6 [M+Na(+)] and on MS:MS fragmented to produce the core lactone ring with m/z of 429.4 and the polyketide side chain of mycolactone A/B with m/z of 359.2. Acetone-soluble lipids from lesions demonstrated significant cytotoxic, pro-apoptotic and anti-inflammatory activities on cultured fibroblast and macrophage cell lines. Mycolactone A/B was detected in all of 10 tissue samples from patients with ulcerative and pre-ulcerative Mu disease.


CONCLUSIONS
Mycolactone can be detected in human tissue infected with Mu. This could have important implications for successful management of Mu infection by antibiotic treatment but further studies are needed to measure its concentration.
Sarfo
Fred Stephen
FS
Komfo Anokye Teaching Hospital, Kumasi, Ghana.
Phillips
Richard O
RO
Rangers
Brian
B
Mahrous
Engy A
EA
Lee
Richard E
RE
Tarelli
Edward
E
Asiedu
Kingsley B
KB
Small
Pamela L
PL
Wansbrough-Jones
Mark H
MH
D000293:Adolescent; D000328:Adult; D000818:Animals; D001427:Bacterial Toxins / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D054312:Buruli Ulcer / Q000378:metabolism* / Q000382:microbiology*; D002460:Cell Line; D002648:Child; D002855:Chromatography, Thin Layer; D005260:Female; D006801:Humans; D018942:Macrolides; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D019911:Mycobacterium ulcerans / Q000378:metabolism* / Q000502:physiology; D012867:Skin / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D021241:Spectrometry, Mass, Electrospray Ionization; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
D001427:Bacterial Toxins; D018942:Macrolides; D014409:Tumor Necrosis Factor-alpha; C117218:mycolactone