Featured Research

from universities, journals, and other organizations

How Salmonella Bacteria Cause Diarrhea In Their Host

Date:
October 17, 2009
Source:
ETH Zurich
Summary:
Salmonella bacteria are cunning when it comes to triggering diarrhea in their host. Researchers have succeeded in explaining a molecular mechanism that enables the bacteria to activate their host cell's non-specific immune response, thus making the host ill. A single virulence factor is sufficient to allow the bacteria to trigger disease.

Illustration of the structure of SopE (blue) bound to the GTPase CdC42.
Credit: Image courtesy of ETH Zurich

Salmonella bacteria are cunning when it comes to triggering diarrhoea in their host. ETH Zurich researchers have succeeded in explaining a molecular mechanism that enables the bacteria to activate their host cell’s non-specific immune response, thus making the host ill. A single virulence factor is sufficient to allow the bacteria to trigger disease.

When Salmonellae gain entry into the gastro-intestinal tract, for example through contaminated egg-based foods such as mayonnaise or tiramisω, their victim’s culinary enjoyment is over. The infection is violent, lasts several days and weakens patients severely. The pathogens themselves are tenacious and can be detected in faeces up to 30 days after the initial infection.

Salmonellae have developed an ingenious mechanism to do this. Some of them penetrate into intestinal epithelium cells, which form the topmost layer of the intestinal tissue. Although the pathogens are killed in these cells, they nonetheless succeed in provoking inflammation that destroys the intestinal flora and nullifies their protective function. Their comrades of the same species that remained in the intestine exploit this and proliferate, and the affected person develops violent diarrhoea.

A completely different function

Scientists led by Wolf-Dietrich Hardt, Professor at the Institute of Microbiology (D-BIOL), have now shown for the first time which molecule is sufficient to trigger the diarrhoeal disease: the protein SopE, which Hardt has studied for a good part of the past 12 years and whose molecular function he determined during his post-doctoral research. However, the biological function of SopE is quite different to what the researchers expected at that time.

The bacteria inject the protein molecule into an intestinal epithelium cell, where it triggers a cascade of signals inside the cell. SopE tampers with two specific GTPases called Cdc42 and Rac1. These molecules are responsible for, among other things, building the cell’s skeleton and thus for the cell’s structure. When SopE binds to these two factors, the cell changes its surface and Salmonellae can penetrate into the cell. Previously, the researchers had assumed that this cell invasion brought about by SopE causes the diarrhoea.

Unexpected immune response

However, Hardt and his research group have now shown that Cdc42 and Rac1 are also a part of the cell’s early warning system. This system is indispensable for a rapid, non-specific defence against disease pathogens. What the two molecules do is to activate, via a route that is still unknown, the molecule Caspase-1, which is a cornerstone of inflammatory responses in the cell and also becomes active in sunburn, for example. Caspase-1 in turn activates chemical messengers that attract phagocytes such as macrophages. These finally put an end to the Salmonellae that penetrated into the intestinal tissue. On the other hand, earlier observations suggest that the Salmonellae that remain in the intestinal lumen can benefit from the resulting inflammation.

The perfidiousness of SopE is that the bacteria tamper with, of all things, a communication system which a cell cannot simply replace or switch off, because otherwise the non-specific immune response would fail to happen or the cell’s skeleton would be paralysed. Consequently, it is also not easy to find an active ingredient that disables Caspase-1, for example, to prevent the infection. Hardt stresses “That would impair the host’s general fitness more severely than the infection by Salmonellae.”

Diarrhoea is the lesser evil

Animals in which Caspase-1 did not function would quickly perish in the wild. This was shown in experiments on mice that lacked Caspase-1. Salmonellae and other disease pathogens infect the internal organs of these animals more severely. Thus the host is in a dilemma: although Caspase-1 allows Salmonellae to cause diarrhoea – allow them to colonise the host’s intestinal lumen more easily – without this protein, an animal or human being would be highly vulnerable to a large number of disease pathogens. Consequently diarrhoea is the lesser of the two evils.

Ironically, not all strains of Salmonella possess SopE. Only certain strains that have incorporated the genetic code for SopE into their own genome from a bacteria-specific virus, a bacteriophage, and can express it, can produce this substance. However, SopE is only one of 12 candidate chemical messengers that Salmonellae use to “crack” their host’s cell. That’s why Hardt’s researchers are now also studying how the other virulence factors operate.


Story Source:

The above story is based on materials provided by ETH Zurich. Note: Materials may be edited for content and length.


Journal Reference:

  1. Mόller et al. The S. Typhimurium Effector SopE Induces Caspase-1 Activation in Stromal Cells to Initiate Gut Inflammation. Cell Host & Microbe, 2009; 6 (2): 125 DOI: 10.1016/j.chom.2009.07.007

Cite This Page:

ETH Zurich. "How Salmonella Bacteria Cause Diarrhea In Their Host." ScienceDaily. ScienceDaily, 17 October 2009. <www.sciencedaily.com/releases/2009/09/090911205127.htm>.
ETH Zurich. (2009, October 17). How Salmonella Bacteria Cause Diarrhea In Their Host. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2009/09/090911205127.htm
ETH Zurich. "How Salmonella Bacteria Cause Diarrhea In Their Host." ScienceDaily. www.sciencedaily.com/releases/2009/09/090911205127.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Dangerous Bacteria Kills One in Florida

Dangerous Bacteria Kills One in Florida

AP (July 31, 2014) — Sarasota County, Florida health officials have issued a warning against eating raw oysters and exposing open wounds to coastal and inland waters after a dangerous bacteria killed one person and made another sick. (July 31) Video provided by AP
Powered by NewsLook.com
Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) — Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Peace Corps Pulls Workers From W. Africa Over Ebola Fears

Peace Corps Pulls Workers From W. Africa Over Ebola Fears

Newsy (July 30, 2014) — The Peace Corps is one of several U.S.-based organizations to pull workers out of West Africa because of the Ebola outbreak. Video provided by Newsy
Powered by NewsLook.com
Weather Kills 2K A Year, But Storms Aren't The Main Offender

Weather Kills 2K A Year, But Storms Aren't The Main Offender

Newsy (July 30, 2014) — Health officials say 2,000 deaths occur each year in the U.S. due to weather, but it's excessive heat and cold that claim the most lives. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

    Environment News

    Technology News



      Save/Print:
      Share:  

      Free Subscriptions


      Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

      Get Social & Mobile


      Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

      Have Feedback?


      Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
      Mobile iPhone Android Web
      Follow Facebook Twitter Google+
      Subscribe RSS Feeds Email Newsletters
      Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins