The Pathogenic Mechanism of the Virulence Factor, Mycolactone, Depends on Blockade of Protein Translocation into the ER

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Buruli ulcer is a progressive necrotic skin lesion caused by infection with the human pathogen Mycobacterium ulcerans. Mycolactone, a small compound produced by the mycobacterium, is the root cause of the disease pathology, but until now there has been no unifying mechanism explaining why. We have been using a model system to investigate the reason for the selective loss of protein that is a common feature of mycolactone exposure. Specifically, this involves identifying the point at which it stops immune cells making inflammatory mediators. In this work, we demonstrate that mycolactone inhibits production of such proteins by blocking the first step of protein export: translocation into a cellular compartment called the endoplasmic reticulum (ER). Proteins due for export are instead made in the cell cytosol where they are recognised as being in the wrong place and are rapidly degraded, causing a general cessation of the production of proteins that have to travel through the ER, including almost all secreted and surface proteins. This has a profound effect on basic cell functions such as growth, adhesion and survival. Therefore, we have identified the molecular basis underlying the key features of Buruli ulcer, and this will transform our understanding of disease progression.

Vyšlo v časopise: The Pathogenic Mechanism of the Virulence Factor, Mycolactone, Depends on Blockade of Protein Translocation into the ER. PLoS Pathog 10(4): e32767. doi:10.1371/journal.ppat.1004061
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004061

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