Researchers Discover How Some Infectious Bacteria Evade Destruction And Survive In Human Cells

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Main Category: Infectious Diseases / Bacteria / Viruses
Also Included In: Biology / Biochemistry
Article Date: 12 Oct 2009 - 11:00 PDT

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Researchers from France and the US have discovered a way in which bacteria that cause disease by invading human cells escape destruction by cellular processes that normally mop up and destroy unwanted foreign agents. The discovery is significant because about one third of human deaths worldwide are due to infectious diseases, some of which are caused by intracellular bacteria (this is more deaths than caused by all forms of cancer combined).

The study was the work of researchers from the Pasteur Institute in Paris, Thomas Jefferson University in Philadelphia, and Yale University in New Haven, Connecticut and is published this week in the open access Public Library of Science journal PLoS one. The study was led by Dr Fabienne Paumet, assistant professor of Microbiology and Immunology at Jefferson Medical College.

Intracellular bacteria include Chlamydia, which causes infertility in women, and Legionella, which causes Legionnaire's disease. These bacteria enter human cells and remain there quite successfully, managing to escape destruction by cellular processes that normally find and destroy pathogens. Until this study it was not clear how they did this.

Paumet and colleagues found that the bacteria expressed SNARE proteins that protected them from destruction. Human cells, like those of many other organisms, use SNARE proteins (short for Soluble NSF Attachment [Protein] REceptors) to help compartments inside cells fuse together while they exchange materials. Thus they play an important role in trafficking of materials into, out of and within cells.

SNARE proteins are found on the surface of nearly all intracellular compartments, and when they interact they create a stable complex that triggers the fusion of the skins around the compartments. One of these compartments is the lysosome, into which pathogens and other foreign agents are conveyed for destruction.

The researchers had a hunch, which they tested, that the SNARE proteins expressed by bacteria like Chlamydia and Legionella were able to interact with the SNARE proteins on the surfaces of the host intracellular compartments and change the ways their membranes fused to their advantage.

Using an in vitro liposome fusion assay and a cellular assay, they showed that SNARE-like bacterial proteins blocked membrane fusion in the intracellular compartments of the host cells.

More specifically, they found that the IncA, the SNARE-like protein expressed by Chlamydia, and IcmG/DotF, the one expressed by Legionella, both directly inhibited the membrane fusing normally triggered by the host cell's SNARE proteins.

As Paumet explained in a statement:

"Based on our results, it seems that intracellular bacteria are able to express 'inhibitory SNAREs' to block fusion between the lysosome and the compartment containing the bacteria."

"The SNARE proteins function like a zipper, and without each half, they can't fuse," said Paumet.

This would suggest that the SNARE-like proteins expressed by bacteria like Chlamydia and Legionella might be a suitable target for new drugs. The drugs would then undermine the bacteria's ability to inhibit those processes that host cells use to destroy them.

"Thorough understanding of the bacterial SNARE-like protein system will give us the necessary tools to design such therapeutics," said Paumet.

"Intracellular Bacteria Encode Inhibitory SNARE-Like Proteins."
Fabienne Paumet, Jordan Wesolowski, Alejandro Garcia-Diaz, Cedric Delevoye, Nathalie Aulner, Howard A. Shuman, Agathe Subtil, James E. Rothman.
PLoS one, October 2009.

Additional source: Thomas Jefferson University.

Written by: Catharine Paddock, PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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