Recent advances: role of mycolactone in the pathogenesis and monitoring of Mycobacterium ulcerans infection/Buruli ulcer disease
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Date
2015-11-13
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Journal ISSN
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Publisher
John Wiley & Sons Ltd
Abstract
Infection 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 lipidlike
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
Description
An article published by John Wiley & Sons Ltd and is available at doi:10.1111/cmi.12547
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Citation
John Wiley & Sons Ltd Cellular Microbiology 18, 17–29