ARCHIVED - A Bacterial Enemy's Enemy Becomes Our Friend
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February 07, 2007— Ottawa, Ontario
Bacteriophages are among the most successful tricksters and traitors of the microbial world, and NRC scientists intend to turn that success into a solution for one of today's most pressing health problems. That problem is the emergence of "superbugs," infectious bacteria that are becoming resistant to all of the antibiotic remedies we have available. Yet many of these same bacteria remain constantly vulnerable to bacteriophages, viruses that can disguise themselves in ways that could enable them to target even the hardiest of superbugs and seal their doom.
Like all viruses, they have developed the ability to take advantage of a host cell. Looking much like a spaceship with landing struts that attach to the surface of the cell, the phage converts that cell's reproductive system to make more copies of itself. The resulting phage then do the same to other cells, and so on.
|Transmission electron micrograph of Campylobacter jejuni bacteriophage whose genome sequence was recently solved. Image provided by John Austin and Greg Sanders, Bureau of Microbial Hazards, Health Canada.|
This is how a virus like the flu spreads within your body, but it is also the way some types of phage specifically attack the kind of bacteria that might otherwise give you a serious infection.
"Bacteriophages have been used as therapeutics in Eastern European societies for many years," says Christine Szymanski, an NRC Institute for Biological Sciences (NRC-IBS) research officer, noting that these agents have often been extracted from the exotic chemical soup found in sewage. "Here in the West, we've been using them more as molecular biology tools rather than therapies. But now people are thinking about this idea, since so many bacterial organisms are becoming resistant to traditionally used antibiotics."
It was a Canadian investigator, Félix d'Hérelle, who first identified bacteriophages, while conducting research at Paris' famous Pasteur Institute in the years after World War I. The discovery eventually enabled some firms to employ particular viruses as treatments for bacterial infections.
|NRC researchers Dr.Christine Szymanski and Dr.Jamshid Tanha|
Dr. Szymanski and her colleague Jamshid Tanha are significantly enhancing this principle through a technique known as protein engineering. Rather than putting entire bacteriophages to work as therapies, they are exploiting specific proteins produced by these viruses. The result is a more limited and controlled application of their potential, limiting the ability of bacteria to colonize the gastrointestinal tract.
Dr. Tanha had previously worked on an antibody project with NRC-IBS and Dow Agrosciences Canada Ltd., aimed at preventing E. coli O157:H7 infections by removing them from the source animals. Szymanski has spent most of her career studying Campylobacter jejuni, the leading cause of bacterial diarrheal illness in Canada, which has proven to be as lethal as E. coli in such notorious outbreaks as Walkerton, Ontario in 2000.
Although bacteriophages were new to both researchers, their combined expertise has proven well suited to the investigations that have been carried out for the last three years in collaboration with Dow Agrosciences. Although Dow is no longer supporting that work, it is helping them patent their findings, which have significant commercial potential. For example, they demonstrated the ability of engineered bacteriophage proteins to limit the colonization of the chicken intestinal tract by bacteria such as Campylobacter and Salmonella.
|Transmission electron micrograph of negatively stained Campylobacter jejuni RM1221 provided by John Austin and Greg Sanders, Bureau of Microbial Hazards, Health Canada.|
Above all, Dr. Szymanski explains, these engineered products are normally directed against bacterial structures needed to cause infections; if the bacteria develop any kind of resistance against these bacteriophage products, the products will likely become compromised. In addition, we are not likely to notice any side effects from these products because they are derived directly from the bacteriophage which is normally found on the foods that we eat and in our intestinal tracts. "These are viruses specific to the bacteria, she stresses. They have no effect on us." Dr. Tanha adds that the investigators quickly learned just how specific these viruses were, as experiments on Campylobacter and Salmonella yielded early and effective results, adding momentum to their plans to study other organisms.
They are also seeking to establish a new collaboration with the Canadian Institutes for Health Research, which recently launched an initiative seeking alternatives to traditional antibiotics. Drs. Tanha and Szymanski are proposing to apply their innovative approach to seek ways of dealing with Clostridium difficile, an opportunistic bacterium that has become quite problematic in many of the country's hospitals.
But there may in fact be no end to the variety of targets. And as long as there are bacteria that can make our lives difficult, we will be driven to find microscopic allies amongst those viruses that choose to make the life of bacteria no less difficult.
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