‘Big Brother’ surveillance stops Salmonella getting stressed out

Scientists from Germany and the UK have discovered how pathogens such as Salmonella respond quickly to stress in its bacterial membrane or “skin”, giving insight into how the bacterium is able to adapt so rapidly to a multitude of harsh environments. Salmonella food poisoning costs the UK economy around £1 billion every year and severe cases can become life threatening for the young and the elderly. The researchers from the Max Planck Institute for Infection Biology and the Institute of Food Research hope that a better understanding of how the pathogen copes with stress will help develop new ways of fighting and preventing infections.

When the bacterium infects its host, it must survive a range of harsh conditions from strong acids in the stomach, to anaerobic and salty environments in the intestine. To adapt to these different conditions, Salmonella must continuously remodel its bacterial “skin” by inserting outer membrane proteins (OMPs) into the cell wall which regulate the transport of salts and allow the bacterium to communicate with its environment. This research, published in the journal Molecular Microbiology, reveals that Salmonella uses a surveillance loop to constantly monitor levels of OMPs to respond fast to signs of stress by switching off protein expression using molecules called small RNAs (sRNAs). These bind to the messenger RNA (mRNA) molecules responsible for the production of OMPs.

“The OMP messenger RNA is unusually stable – it has a half-life of around 15 minutes compared with 5 minutes for other Salmonella mRNAs so it was a mystery how the bacterium could switch off OMP production so quickly” explains Professor Jay Hinton of the Institute of Food Research, “We discovered that a different type of RNA called sRNA binds to the OMP mRNA and blocks its action. The cell then degrades the resulting double stranded RNA molecule. Our novel finding is that these sRNAs called RybB and MicA are able to bind to so many different types of OMP mRNA molecule – most sRNAs bind to only one type.”

The research, supported by the Biotechnology and Biological Sciences Research Council (BBSRC), used a revolutionary new approach combining bioinformatics techniques with cutting edge microarray technology to first identify the sRNAs and then search the 5000 genes in the Salmonella genome for the targets to which they bind. The researchers then confirmed these results by studying a mutant strain lacking the sRNA mechanism.

“We call this a surveillance loop because it allows Salmonella to be constantly vigilant, just like George Orwell’s Big Brother” says Dr Joerg Vogel who led the research at the Max Planck Institute for Infection Biology. “As soon as a problem is detected, the bacterium responds in the same way as the police upon witnessing a crime on CCTV; in this case these small RNAs are deployed, rather than policemen. If Salmonella cannot detect and deal with the problem, however, it becomes extremely stressed.”

Researchers are hoping to apply the same technologies to other pathogenic bacteria. This knowledge could be used in the future to exploit the weaknesses of these dangerous bacteria and to help develop new antibacterials to combat infections when current antibiotics stop working. The proportion of Salmonella bacteria that are resistant to current antibiotics is increasing each year.

This research is particularly relevant as Christmas approaches; whilst only 1 in 20 of turkeys sold for meat in the UK are contaminated with Salmonella, two-thirds of these bacteria are resistant to one or more antibiotics, although researchers stress there is no danger to health if the meat is properly cooked. It is likely that the new surveillance loop discovered here is one of the tools that allow Salmonella to be so successful at infecting both animals and humans.

Notes to Editors:
Contacts:
Catherine Reynolds, Norwich BioScience Institutes Press Office: +44 (0)1603 255217, catherine.reynolds@ifr.ac.uk
Sabine Englich, Max Planck Institute, englich@mpiib-berlin.mpg.de

About the IFR
The mission of the Institute of Food Research (www.ifr.ac.uk) is to undertake international quality scientific research relevant to food and human health and to work in partnership with others to provide underpinning science for consumers, policy makers, the food industry and academia. It is a company limited by guarantee, with charitable status, grant aided by the Biotechnology and Biological Sciences Research Council (www.bbsrc.ac.uk).

About the Max-Planck-Institute for Infection Biology
The main focus of the Max-Planck-Institute for Infection Biology is the basic understanding of the molecular and cellular mechanisms of infection employing multi-disciplinary approaches to infection biology, comprising concepts and methodologies of molecular genetics, immunology, cell biology, epidemiology, clinical research and protein chemistry. The Institute promotes the applications of its research towards paving the way for the design of rational measures of control of infectious diseases.

The Institute is one of the eighty research Institutes of the Max-Planck Society for the Advancement of Science, an independent, non–profit research organization performing basic research in the interest of the general public in the natural sciences, social sciences and the humanities.
www.mpiib-berlin.mpg.de

Reference
Papenfort et al., “sE-dependent sRNAs of Salmonella respond to membrane stress by accelerating global omp mRNA decay” is published in Molecular Microbiology (Dec 2006), volume 62, issue 6, pages 1674-1688.

Salmonella Facts:

Since the beginning of the 1990s, strains of Salmonella enterica sv. Typhimurium resistant to a range of antibiotics have emerged and are threatening to become a serious public health problem, particularly in developing countries.
Since 1885, a total of 2213 types of Salmonella have been identified. They vary in the severity of illness they cause.
Symptoms of salmonellosis (food poisoning caused by Salmonella) are fever, headache, abdominal pain, diarrhoea, nausea and vomiting, and are usually self-limiting after a week. In some cases, particularly in the young and very elderly, dehydration can become severe and life threatening.
Salmonella Typhimurium can be found in a broad range of animals, birds and reptiles as well as the environment. It causes food poisoning in humans mainly through the consumption of raw or undercooked contaminated food of animal origin - especially poultry, eggs, meat, salad vegetables and milk.

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