New Discovery about Salmonella Gene Control Could Help To Develop New Ways to Kill Bacteria

Posted on: 22 July 2009

Scientists from Ireland, the UK and Germany have discovered a new type of gene regulation in Salmonella that gives new insight into the causes of bacterial infection. The discovery of this new mechanism of gene regulation could eventually lead to the development of innovative therapies and reduce the levels of disease caused by Salmonella.

Salmonella causes food poisoning and kills around 1 million people worldwide every year. The bacteria are particularly effective at causing human infection because they can survive a series of harsh conditions which include strong acids in the stomach and the anaerobic and salty environment of the intestine that kill most bacteria.

To survive, Salmonella genes are switched on and off quickly inside the human body in reaction to these harsh conditions. This process involves continuous remodelling of the bacterial surface by adding outer membrane proteins (OMPs) to the cell wall to cope with the new environment.

The exciting research by scientists from Trinity College Dublin, the Institute of Food Research in the UK and the Max Planck Institute for Infection Biology just published in the journal Nature Structural & Molecular Biology, reveals a new mechanism used by Salmonella to control levels of a particular OMP (OmpD) by molecules called small RNAs (sRNAs). sRNAs bind to the messenger RNA (mRNA) that is responsible for making the protein. OmpD is a vital surface protein that allows Salmonella to survive salty environments and to kill people.
 
Professor Jay Hinton, Stokes Professor of Microbial Pathogenesis, Trinity College Dublin said:  “We discovered that an sRNA called MicC can switch off a protein by binding to mRNA with a new and unexpected mechanism. Until now, binding of sRNAs was thought to be limited to just 1% of the bacterial chromosome. We discovered that the MicC sRNA can bind at any position within a gene’s mRNA”.
 
“Because MicC can bind to virtually anywhere on the chromosome it provides Salmonella with an efficient method of switching off proteins such as OMPs. By controlling OmpD, MicC helps Salmonella to thrive in salty conditions and to infect humans. This mechanism solves a long-standing mystery, because it had been thought that bacteria only used sRNAs in a primitive way. Our discovery unifies a whole area of biology – now we know that bacteria can use the same sophisticated mechanism found in plants and animals”.
 
“This breakthrough reveals another tactic that Salmonella uses to cause disease. We hope that in the future scientists will be able to use the findings to develop new ways to kill Salmonella. It is an exciting step on the path of reducing the levels of Salmonella and reducing human disease worldwide,”  concluded Professor Hinton.

The research, supported by the Science Foundation Ireland, the Biotechnology and Biological Sciences Research Council (BBSRC) and the Deutsche Forschungsgemeinschaft, used cutting edge microarray technology to search the 5000 genes in the Salmonella genome for the targets to which the MicC sRNA bound. The researchers then confirmed these results by a combination of biochemistry and molecular biology.

This study is particularly relevant in the summer time when the level of Salmonella-associated food poisoning increases during the barbecue season, and 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.

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.

– 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 – including poultry, eggs, meat, and milk, and also salad vegetables.