Indolent Cutaneous Ulceration Due to Infection With Mycobacterium Ulcerans

Forbes, B. R. V.; Wannan, J. S.; Kirkland, W. B.

doi:10.5694/j.1326-5377.1954.tb85518.x

Cited by 27 publications

(15 citation statements)

References 6 publications

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“…In the past 15 years, significant clusters of cases have occurred on Phillip Island 9 and the Mornington and Bellarine Peninsulas near Melbourne (Box 3). Despite this wide distribution, no cases have been reported previously from NSW, except in patients who were exposed during interstate or overseas travel 10 …”

Section: Discussionmentioning

confidence: 99%

First case of Mycobacterium ulcerans disease (Bairnsdale or Buruli ulcer) acquired in New South Wales

Lavender

Senanayake

Fyfe

et al. 2007

Medical Journal of Australia

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Section: Discussionmentioning

confidence: 99%

First case of Mycobacterium ulcerans disease (Bairnsdale or Buruli ulcer) acquired in New South Wales

Lavender

Senanayake

Fyfe

et al. 2007

Medical Journal of Australia

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“…Mycolactone caused cytopathic effects on cultured L929 murine fibroblasts and inoculation of purified mycolactone into guinea pigs intradermally also produced lesions that were histologically like BU with necrosis of subcutaneous fat . In contrast to other pathogenic mycobacteria, which are intracellular pathogens of macrophages, histology of MU lesion finds extracellular clusters of MU bacilli lying within areas of coagulative necrosis that extend some distance from the site of bacterial colonization . Nevertheless, inoculation of an isogenic toxin‐negative mutant of MU caused a granulomatous lesion typical of the inflammatory response to other mycobacteria with phagocytozed MU visible within macrophages and none of the characteristic fat necrosis …”

Section: Immune Suppression Associated With Bu Diseasementioning

confidence: 99%

Challenges associated with the treatment of Buruli ulcer

Aboagye

Kpeli

Tuffour³

et al. 2018

Journal of Leukocyte Biology

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Buruli ulcer (BU), caused by Mycobacterium ulcerans (MU), is the third most important mycobacterial diseases after tuberculosis and leprosy in immunocompetent individuals. Although the mode of transmission remains an enigma, disease incidence has been strongly linked to disturbed environment and wetlands. The blunt of the diseases is recorded in West African countries along the Gulf of Guinea, and children 15 years and below account for about 48% of all cases globally. Prior to 2004, wide surgical excisions and debridement of infected necrotic tissues followed by skin grafting was the accepted definitive treatment of BU. However, introduction of antibiotic therapy, daily oral rifampicin (10 mg/kg) plus intramuscular injection of streptomycin (15 mg/kg), for 8 weeks by the WHO in 2004 has reduced surgery as an adjunct for correction of deformities and improved wound healing. An all-oral regimen is currently on clinical trial to replace the injectable. It is thought that a protective cloud of the cytotoxic toxin mycolactone kills infiltrating leucocytes leading to local immunosuppression and down-regulation of the systemic immune system. Our studies of lesions from BU patients treated with SR have demonstrated treatment-associated initiation of vigorous immune responses and the development of ectopic lymphoid tissue in the BU lesions. Despite these interventions, there are still challenges that bedevil the management of BU including paradoxical reactions, evolution of lesions after therapy, prolong viability of MU in BU lesions, and development of secondary bacterial infection. In this paper, we will mainly focus on the critical and pertinent challenges that undermine BU treatment toward effective control of BU.

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“…Over a few weeks, these lesions break down to form characteristic ulcers with undermined edges, which are associated with extensive necrosis alongside minimal inflammatory response. In contrast to other pathogenic mycobacteria, which are facultative intracellular pathogens of macrophages, MU is seen as extracellular clusters of bacilli lying within areas of coagulative necrosis that extend some distance from the site of bacterial colonisation (Forbes et al, 1954). This observation led to early proposals that MU secretes an exotoxin (Connor et al, 1965;Connor et al, 1966).…”

Section: Introductionmentioning

confidence: 99%

Recent advances: role of mycolactone in the pathogenesis and monitoring ofMycobacterium ulceransinfection/Buruli ulcer disease

Sarfo

Phillips

Wansbrough‐Jones

et al. 2015

Cellular Microbiology

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SummaryInfection of subcutaneous tissue with Mycobacterium ulcerans can lead to chronic skin ulceration known as Buruli ulcer. The pathogenesis of this neglected tropical disease is dependent on a lipid‐like toxin, mycolactone, which diffuses through tissue away from the infecting organisms. Since its identification in 1999, this molecule has been intensely studied to elucidate its cytotoxic and immunosuppressive properties. Two recent major advances identifying the underlying molecular targets for mycolactone have been described. First, it can target scaffolding proteins (such as Wiskott Aldrich Syndrome Protein), which control actin dynamics in adherent cells and therefore lead to detachment and cell death by anoikis. Second, it prevents the co‐translational translocation (and therefore production) of many proteins that pass through the endoplasmic reticulum for secretion or placement in cell membranes. These pleiotropic effects underpin the range of cell‐specific functional defects in immune and other cells that contact mycolactone during infection. The dose and duration of mycolactone exposure for these different cells explains tissue necrosis and the paucity of immune cells in the ulcers. This review discusses recent advances in the field, revisits older findings in this context and highlights current developments in structure‐function studies as well as methodology that make mycolactone a promising diagnostic biomarker.

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Indolent Cutaneous Ulceration Due to Infection With Mycobacterium Ulcerans

Cited by 27 publications

References 6 publications

First case of Mycobacterium ulcerans disease (Bairnsdale or Buruli ulcer) acquired in New South Wales

First case of Mycobacterium ulcerans disease (Bairnsdale or Buruli ulcer) acquired in New South Wales

Challenges associated with the treatment of Buruli ulcer

Recent advances: role of mycolactone in the pathogenesis and monitoring ofMycobacterium ulceransinfection/Buruli ulcer disease

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