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RTD info logoMagazine on European Research N° 45 - May 2005   
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HEALTH RISKS
Title  Campylobacteria under the microscope

Campylobacteria are the primary cause of a vast range of food infections worldwide. Yet we know surprisingly little about them and the tools for isolating, cultivating and describing them are inadequate. A consortium of European, South African and American scientists recently undertook to pursue research into this unjustifiably neglected microbial family and to evaluate its potentially infectious impact.

Helicobacter pylori is the new name for Campylobacter pylori, whose pathogenic role in certain forms of gastritis and duodenal ulcers was recently identified.  © A. Labigne/ Institut Pasteur
Helicobacter pyloriis the new name for Campylobacter pylori, whose pathogenic role in certain forms of gastritis and duodenal ulcers was recently identified.
© A. Labigne/ Institut Pasteur
Around 4 000 species of bacteria have been identified to date, but nobody knows how many really inhabit the Earth. Yet a better knowledge of the biodiversity of the bacterial world has implications that extend far beyond fundamental microbiology as it could help us identify the culprits behind infectious diseases, particularly those of food origin.

Given that the causes of the vast majority of sometimes serious food infections remain unknown, the Campycheck project is of major importance. It aims to study the biodiversity of campylobacteria, a group of bacteria that are presumed responsible for around 600 million infections worldwide every year. This is applied research in the field of food safety.

Campylobacteria are bacteria in the shape of curved rods. They inhabit the digestive tract of animals – on farms and in the wild – and prefer oxygen-poor environments, some of them tolerating strictly anaerobic conditions. They are pathogenic in man, affecting mainly children and young adults and causing severe diarrhoea which, in turn, can lead to complications such as intestinal haemorrhage or generalised infection. In some – fortunately rare – cases, they develop into a serious neurological syndrome: in Guillain-Barré disease, the antibodies the organism secretes to combat the infection subsequently attack neurons, leading to general paralysis.

Contamination can be either from direct contact with animal excrement, polluted water, or – most commonly – consumption of contaminated foods such as chicken, pork or mutton which have been cleaned inadequately in abattoirs, and also unwashed vegetables, unpasteurised milk, etc.  

Two culprits?
Intracellular motility of the Shigella bacteria which invades and destroys the intestinal mucous of the colon, causing diarrhoea. It moves around the infected cell and propagates in neighbouring cells by creating a tail of polymerised actin.  © J.P.Sansonetti/Inserm
Intracellular motility of the Shigella bacteria which invades and destroys the intestinal mucous of the colon, causing diarrhoea. It moves around the infected cell and propagates in neighbouring cells by creating a tail of polymerised actin.
© J.P.Sansonetti/ Inserm
Although we are aware of about 30 campylobacteria varieties, research to date has focused almost exclusively on just two of them: Campylobacteria jejuni and Campylobacteria coli. This is because C. jejuni and C. coli have traditionally been identified as the ‘presumed culprits’ of 99% of infections attributable to this microbial family. “All present procedures are designed to investigate these two targets that are able to survive at temperatures of 42°C,” explains William Keevil of Southampton University (UK), the Campycheck coordinator. “Standardised and effective methods for detecting them are now available, thanks in particular to the Campynet programme, a network of 23 European laboratories supported by the European Union between 1998 and 2001.” 

The Campycheck project promoters believe, however, that researchers have been rather too quick to jump to conclusions in identifying the guilty parties. They take the view that, due to insufficient monitoring, we know little about the real prevalence of infections caused by campylobacteria. No figures are available for Europe, for example. In the United States, the Centre for Disease Control in Atlanta reports around 10 000 cases a year, about 100 of them proving fatal – but estimates that the actual number of infections annually is around 2 to 4 million, making this the main cause of food poisoning, ahead of salmonella! 

Why is there this discrepancy? “Infections by campylobacteria are generally sporadic and rarely result in epidemics, as a result of which research on methods of contamination has been rather neglected,” explains William Keevil. “But there is also a lack of scientific knowledge. Our hypothesis is that there are many campylobacteria species which we are unable to detect. These emerging varieties could be responsible for many illnesses wrongly attributed to C. jejuni and C. coli. So much remains to be done in this field. In particular, we must develop tests able to identify non-thermo-tolerant bacteria.” 

A transcontinental affair
The intestinal wall forms multiple folds covered in villi: this picture shows the upper section (apex) of the absorbent polygonal cells that constitute the villi of the small intestine. It is these cells that absorb food. Size: 0.1 mm in diameter per villus. © C.Haffen/Inserm
The intestinal wall forms multiple folds covered in villi: this picture shows the upper section (apex) of the absorbent polygonal cells that constitute the villi of the small intestine. It is these cells that absorb food. Size: 0.1 mm in diameter per villus.
© C.Haffen/Inserm
Isolating, describing and detecting these unlisted campylobacteria is essentially the role of Campycheck, an association that includes, in addition to Southampton University, the Irish National Food Authority’s laboratory, Cape University (South Africa), the University of Bologna (Italy), the Danish Veterinary Institute, and the US Department of Agriculture, representing three continents. “The aim of the project came from a conversation in the United States with Al Lastovica of Cape University, a world-renowned specialist on this bacterial family,” explains William Keevil. "This global research structure is justified by the fact that the threat posed by campylobacteria, which could be carried by migrating birds, really has to be approached on a planetary basis. This is particularly vital at a time when we are seeing an increase in trade in foodstuffs between different continents.” 

The first task the researchers have set themselves is to acquire new tools with which to explore this largely unknown microbial world, such as low-oxygenated culture media, monoclonal antibodies able to detect proteins common to all campylobacteria varieties, and Polymerase Chain Reaction (PCR) kits able to distinguish between species and sub-species. The aim is to develop campylobacteria detection tests that can be applied in the fields of human medicine (analysis of blood diseases), veterinary medicine (on the basis of excrement obtained from farms), and health safety (food or drinking water samples). 

The likely economic benefits of this innovative work are illustrated by the presence, as project partners, of two British biotechnology companies specialising in microbiological biodiagnostics – Microgen Bioproducts Ltd (Camberley, Surrey) and Oxoid Ltd (Basingstoke, Hampshire).   

"Eighteen months after start-up, we have the tools needed to isolate and characterise emerging campylobacteria,” says the coordinator. “A number of US, Asian and European laboratories have contacted us, which shows the interest in the various aspects of our programme.”

For health protection
However, the Campycheck project extends beyond this research and technological development activity. In the field of fundamental microbiology, campylobacteria obtained from the three continents on which the programme partners are based (Europe, Africa, North America) will be pooled and analysed genetically. The collection at the Stephen On laboratory at the Danish Veterinary Institute already contains around 60 strains and many remain to be described and classified. 

Our knowledge of microbial biodiversity, which is patchy to say the least, will be boosted directly from this. But it is in the field of public health that the most benefits are expected. In co-operation with the food safety authorities in a number of countries, Campycheck plans to undertake an epidemiological study of the prevalence of campylobacteria at various stages in the food chain, from ‘farm to fork’. “The project’s ultimate aim is to obtain a risk management model that will make it possible to discover whether or not new and emerging varieties of campylobacteria carry a risk on the same scale as C. jejuni,” concludes William Keevil.


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