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Science. 2012 Jan 20;335(6066):332-5. doi: 10.1126/science.1215930.

Manganese blocks intracellular trafficking of Shiga toxin and protects against Shiga toxicosis.

Author information

1
Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA.

Abstract

Infections with Shiga toxin (STx)-producing bacteria cause more than a million deaths each year and have no definitive treatment. To exert its cytotoxic effect, STx invades cells through retrograde membrane trafficking, escaping the lysosomal degradative pathway. We found that the widely available metal manganese (Mn(2+)) blocked endosome-to-Golgi trafficking of STx and caused its degradation in lysosomes. Mn(2+) targeted the cycling Golgi protein GPP130, which STx bound in control cells during sorting into Golgi-directed endosomal tubules that bypass lysosomes. In tissue culture cells, treatment with Mn(2+) yielded a protection factor of 3800 against STx-induced cell death. Furthermore, mice injected with nontoxic doses of Mn(2+) were completely resistant to a lethal STx challenge. Thus, Mn(2+) may represent a low-cost therapeutic agent for the treatment of STx infections.

PMID:
22267811
PMCID:
PMC5367627
DOI:
10.1126/science.1215930
[Indexed for MEDLINE]
Free PMC Article

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