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Recent advances: role of mycolactone in the pathogenesis and monitoring of Mycobacterium ulcerans infection/Buruli ulcer disease.

Sarfo, FS, Phillips, R, Wansbrough-Jones, M and Simmonds, RE (2016) Recent advances: role of mycolactone in the pathogenesis and monitoring of Mycobacterium ulcerans infection/Buruli ulcer disease. Cell Microbiol, 18 (1). pp. 17-29.

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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 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.

Item Type: Article
Subjects : Microbiology
Divisions : Faculty of Health and Medical Sciences
Authors :
AuthorsEmailORCID
Sarfo, FSUNSPECIFIEDUNSPECIFIED
Phillips, RUNSPECIFIEDUNSPECIFIED
Wansbrough-Jones, MUNSPECIFIEDUNSPECIFIED
Simmonds, REUNSPECIFIEDUNSPECIFIED
Date : January 2016
Identification Number : 10.1111/cmi.12547
Related URLs :
Additional Information : © 2015 The Authors. Cellular Microbiology Published by John Wiley & Sons Ltd This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Depositing User : Symplectic Elements
Date Deposited : 09 Mar 2016 10:46
Last Modified : 09 Mar 2016 10:46
URI: http://epubs.surrey.ac.uk/id/eprint/810047

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