After initiating a collaboration a few
years ago with Professor Jaana Bamford, a colleague at Jyväskylä, Sundberg and the research team were able to isolate a bacteriophage, or phage for short, which feeds
parasitically exist within fish, phages are micro-parasites
that co-exist with the
bacteria. And, akin to them, they can infect and replicate within their host, and outnumber it tenfold. “We noticed that, once we cultured the bacteria and the phage
together, the bacteria actually
changed and became less virulent,” says Sundberg. On the basis of this observation, the researchers decided to examine whether the phages could be used to convert virulent bacteria into non- virulent forms. “Since we first isolated the relevant phages, we set a long term to goal to develop this promising phage-host relationship, and create techniques which could ultimately kill harmful bacteria in the fish-farming environment.” “Phages are always present wherever their hosts,
the bacteria, are,” continues
Sundberg. “The evolution of antibiotic resistant bacteria has led to a great deal of media exposure concerning the possibility of using phages as remedies in human beings. Before antibiotics were developed, they were viewed as a promising treatment for bacterial disease. Following Fleming’s discovery of antibiotics – which have a broader range, and are thus applicable to more diseases – therapies based on these organisms decreased in usage. However, they’re currently undergoing something of a renaissance as medicinal agents. There are already a few companies attempting to pilot phage-based methodologies that can be used in human physiology.” The principle behind Sundberg’s own
proposed technique is to isolate phages in a fish farm, enrich them in a lab, and then return them to aquaculture facilities. “The phages could simply be added to the water of the tanks holding the fish, and would begin to selectively interact with the pathogenic bacteria therein,” she states. “Moreover, because some young fish which can be infected by Flavobacterium columnare are reared in low volumes of water, the amount of phage needed to treat them effectively would be comparatively low, making this a convenient measure”. Within an earlier study, the scientist and
her colleagues were able to experiment on zebrafish, which were infected with Flavobacterium columnare with phages.
and treated
www.projectsmagazine.eu.com
In the 2012 paper reporting their findings, upon it. Much as bacteria
titled Phage-Driven Loss of Virulence in a Fish Pathogenic Bacterium, Sundberg and her co-authors observed that the relationship between phage and bacteria is a parallel “continuous arms race”,
in which bacteria
must evolve to avoid extinction. Their experiments found that certain types of phages were in fact able to neutralise the virulence of targeted bacteria, leading to a drastically reduced disease rate amongst test subjects. Another important result, which helps to explain this impressive impact, was that phages seemed to inhibit the ability of the bacteria to move under their own power. This characteristic, known as gliding motility, is often associated with virulence and, once incapacitated, appeared to limit their potency.
AT A GLANCE Project Information
Project Title: Bacterial virulence and phage-host interactions
Project Objective: The project studies host-pathogen relationship and factors that contribute to virulence using fish, its bacterial pathogen, and virus parasitizing the bacterium as model organisms. The long-term aim of the project is to understand factors selecting for high virulence of pathogens and to develop phage therapy to manage bacterial diseases.
MAIN CONTACT
“We noticed that, once we cultured the bacteria and the phage together, the bacteria actually changed and became less virulent”
According to Sundberg, the 2012 study had
several groundbreaking aspects. It provided the first documented evidence showing the effects of phage-host interactions on this commercially important fish pathogen, and, promisingly, their effectiveness in constraining malign bacteria. The next challenge for the Finnish team is to pursue the opportunities created by this exciting discovery, as well as to refine treatments that fully exploit it. “Using fish to trial different types of
phages is very helpful, since this allows us to find efficient ways of preventing columnaris infections, as well as establishing what the virulent properties of the bacteria are,” explains Sundberg. “To develop effective remedies, it’s critical for us to learn more about the attributes which make bacteria infective within the fish, and also distinguish between virulent and non-virulent strains. This may seem like a rather academic interest, but looking at how phage therapy
Lotta-Riina Sundberg Since gaining PhD in 2007 Sundberg has been interested on host-pathogen relationship and virulence evolution. After research on these themes during the post doc periods, she now works as an Academy Research Fellow in Centre of Excellence in Biological interactions, University of Jyväskylä, and continues the studies with her research group.
Contact: Tel: +358408053931 Email:
lotta-riina.sundberg@
jyu.fi Web: (Personal)
www.lrsundberg.
weebly.com (University)
www.jyu.fi
could be used in real-life systems is a practical dimension central to our work. The results we’ve obtained so far imply that our research could prove very fruitful for disease management at fish farm settings. Ultimately, we hope that it could not only prove applicable to aquaculture, but also suggest new opportunities to use phage therapies to treat other organisms and the bacteria afflicting them.”
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