Change search
ReferencesLink to record
Permanent link

Direct link
The Host-Encoded Heme Regulated Inhibitor (HRI) Facilitates Virulence-Associated Activities of Bacterial Pathogens
Show others and affiliations
2013 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 8, no 7, e68754- p.Article in journal (Refereed) Published
Abstract [en]

Here we show that cells lacking the heme-regulated inhibitor (HRI) are highly resistant to infection by bacterial pathogens. By examining the infection process in wild-type and HRI null cells, we found that HRI is required for pathogens to execute their virulence-associated cellular activities. Specifically, unlike wild-type cells, HRI null cells infected with the gram-negative bacterial pathogen Yersinia are essentially impervious to the cytoskeleton-damaging effects of the Yop virulence factors. This effect is due to reduced functioning of the Yersinia type 3 secretion (T3S) system which injects virulence factors directly into the host cell cytosol. Reduced T3S activity is also observed in HRI null cells infected with the bacterial pathogen Chlamydia which results in a dramatic reduction in its intracellular proliferation. We go on to show that a HRI-mediated process plays a central role in the cellular infection cycle of the Gram-positive pathogen Listeria. For this pathogen, HRI is required for the post-invasion trafficking of the bacterium to the infected host cytosol. Thus by depriving Listeria of its intracellular niche, there is a highly reduced proliferation of Listeria in HRI null cells. We provide evidence that these infection-associated functions of HRI (an eIF2 alpha kinase) are independent of its activity as a regulator of protein synthesis. This is the first report of a host factor whose absence interferes with the function of T3S secretion and cytosolic access by pathogens and makes HRI an excellent target for inhibitors due to its broad virulence-associated activities.

Place, publisher, year, edition, pages
2013. Vol. 8, no 7, e68754- p.
National Category
Cell and Molecular Biology
URN: urn:nbn:se:umu:diva-79608DOI: 10.1371/journal.pone.0068754ISI: 000321765300065OAI: diva2:656932
Available from: 2013-10-17 Created: 2013-08-26 Last updated: 2013-10-17Bibliographically approved

Open Access in DiVA

fulltext(752 kB)98 downloads
File information
File name FULLTEXT01.pdfFile size 752 kBChecksum SHA-512
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Search in DiVA

By author/editor
Rosqvist, Roland
By organisation
Department of Molecular Biology (Faculty of Science and Technology)
In the same journal
Cell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 98 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 52 hits
ReferencesLink to record
Permanent link

Direct link